Combining a Fusion Inhibitory Peptide Targeting the MERS-CoV S2 Protein HR1 Domain and a Neutralizing Antibody Specific for the S1 Protein Receptor-Binding Domain (RBD) Showed Potent Synergism against Pseudotyped MERS-CoV with or without Mutations in RBD
Identifieur interne : 001213 ( Pmc/Curation ); précédent : 001212; suivant : 001214Combining a Fusion Inhibitory Peptide Targeting the MERS-CoV S2 Protein HR1 Domain and a Neutralizing Antibody Specific for the S1 Protein Receptor-Binding Domain (RBD) Showed Potent Synergism against Pseudotyped MERS-CoV with or without Mutations in RBD
Auteurs : Cong Wang ; Chen Hua ; Shuai Xia ; Weihua Li ; Lu Lu ; Shibo JiangSource :
- Viruses [ 1999-4915 ] ; 2019.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) has continuously posed a threat to public health worldwide, yet no therapeutics or vaccines are currently available to prevent or treat MERS-CoV infection. We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, m336 was found to have reduced efficacy against MERS-CoV strains with mutations in RBD, and HR2P-M2 showed low potency, thus limiting the clinical application of each when administered separately. However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. Thus, this combinatorial strategy could be used in clinics for the urgent treatment of MERS-CoV-infected patients.
Url:
DOI: 10.3390/v11010031
PubMed: 30621343
PubMed Central: 6356712
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Combining a Fusion Inhibitory Peptide Targeting the MERS-CoV S2 Protein HR1 Domain and a Neutralizing Antibody Specific for the S1 Protein Receptor-Binding Domain (RBD) Showed Potent Synergism against Pseudotyped MERS-CoV with or without Mutations in RBD</title><author><name sortKey="Wang, Cong" sort="Wang, Cong" uniqKey="Wang C" first="Cong" last="Wang">Cong Wang</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation></author><author><name sortKey="Hua, Chen" sort="Hua, Chen" uniqKey="Hua C" first="Chen" last="Hua">Chen Hua</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation></author><author><name sortKey="Xia, Shuai" sort="Xia, Shuai" uniqKey="Xia S" first="Shuai" last="Xia">Shuai Xia</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation></author><author><name sortKey="Li, Weihua" sort="Li, Weihua" uniqKey="Li W" first="Weihua" last="Li">Weihua Li</name><affiliation><nlm:aff id="af2-viruses-11-00031">NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China;<email>weihua.li@sippr.org.cn</email></nlm:aff></affiliation></author><author><name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-viruses-11-00031">NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China;<email>weihua.li@sippr.org.cn</email></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30621343</idno><idno type="pmc">6356712</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356712</idno><idno type="RBID">PMC:6356712</idno><idno type="doi">10.3390/v11010031</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">001213</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001213</idno><idno 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(S.X.)</nlm:aff></affiliation></author><author><name sortKey="Hua, Chen" sort="Hua, Chen" uniqKey="Hua C" first="Chen" last="Hua">Chen Hua</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation></author><author><name sortKey="Xia, Shuai" sort="Xia, Shuai" uniqKey="Xia S" first="Shuai" last="Xia">Shuai Xia</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation></author><author><name sortKey="Li, Weihua" sort="Li, Weihua" uniqKey="Li W" first="Weihua" last="Li">Weihua Li</name><affiliation><nlm:aff id="af2-viruses-11-00031">NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China;<email>weihua.li@sippr.org.cn</email></nlm:aff></affiliation></author><author><name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-viruses-11-00031">NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China;<email>weihua.li@sippr.org.cn</email></nlm:aff></affiliation></author></analytic><series><title level="j">Viruses</title><idno type="eISSN">1999-4915</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) has continuously posed a threat to public health worldwide, yet no therapeutics or vaccines are currently available to prevent or treat MERS-CoV infection. We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, m336 was found to have reduced efficacy against MERS-CoV strains with mutations in RBD, and HR2P-M2 showed low potency, thus limiting the clinical application of each when administered separately. However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Viruses</journal-id><journal-id journal-id-type="iso-abbrev">Viruses</journal-id><journal-id journal-id-type="publisher-id">viruses</journal-id><journal-title-group><journal-title>Viruses</journal-title></journal-title-group><issn pub-type="epub">1999-4915</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">30621343</article-id><article-id pub-id-type="pmc">6356712</article-id><article-id pub-id-type="doi">10.3390/v11010031</article-id><article-id pub-id-type="publisher-id">viruses-11-00031</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Combining a Fusion Inhibitory Peptide Targeting the MERS-CoV S2 Protein HR1 Domain and a Neutralizing Antibody Specific for the S1 Protein Receptor-Binding Domain (RBD) Showed Potent Synergism against Pseudotyped MERS-CoV with or without Mutations in RBD</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Cong</given-names></name><xref ref-type="aff" rid="af1-viruses-11-00031">1</xref><xref ref-type="author-notes" rid="fn1-viruses-11-00031">†</xref></contrib><contrib contrib-type="author"><name><surname>Hua</surname><given-names>Chen</given-names></name><xref ref-type="aff" rid="af1-viruses-11-00031">1</xref><xref ref-type="author-notes" rid="fn1-viruses-11-00031">†</xref></contrib><contrib contrib-type="author"><name><surname>Xia</surname><given-names>Shuai</given-names></name><xref ref-type="aff" rid="af1-viruses-11-00031">1</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Weihua</given-names></name><xref ref-type="aff" rid="af2-viruses-11-00031">2</xref></contrib><contrib contrib-type="author"><name><surname>Lu</surname><given-names>Lu</given-names></name><xref ref-type="aff" rid="af1-viruses-11-00031">1</xref><xref rid="c1-viruses-11-00031" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><name><surname>Jiang</surname><given-names>Shibo</given-names></name><xref ref-type="aff" rid="af1-viruses-11-00031">1</xref><xref ref-type="aff" rid="af2-viruses-11-00031">2</xref><xref rid="c1-viruses-11-00031" ref-type="corresp">*</xref></contrib></contrib-group><aff id="af1-viruses-11-00031"><label>1</label>Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</aff><aff id="af2-viruses-11-00031"><label>2</label>NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China;<email>weihua.li@sippr.org.cn</email></aff><author-notes><corresp id="c1-viruses-11-00031"><label>*</label>Correspondence: <email>lul@fudan.edu.cn</email> (L.L.); <email>shibojiang@fudan.edu.cn</email> (S.J.); Tel.: +86-21-5423-7673 (L.L.); +86-21-5423-7673 (S.J.)</corresp><fn id="fn1-viruses-11-00031"><label>†</label><p>These authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="epub"><day>06</day><month>1</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>1</month><year>2019</year></pub-date><volume>11</volume><issue>1</issue><elocation-id>31</elocation-id><history><date date-type="received"><day>09</day><month>12</month><year>2018</year></date><date date-type="accepted"><day>02</day><month>1</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 by the authors.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Middle East respiratory syndrome coronavirus (MERS-CoV) has continuously posed a threat to public health worldwide, yet no therapeutics or vaccines are currently available to prevent or treat MERS-CoV infection. We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, m336 was found to have reduced efficacy against MERS-CoV strains with mutations in RBD, and HR2P-M2 showed low potency, thus limiting the clinical application of each when administered separately. However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. Thus, this combinatorial strategy could be used in clinics for the urgent treatment of MERS-CoV-infected patients.</p></abstract><kwd-group><kwd>MERS-CoV</kwd><kwd>RBD</kwd><kwd>mutation</kwd><kwd>peptide</kwd><kwd>neutralizing antibody</kwd><kwd>combination</kwd></kwd-group></article-meta></front><floats-group><fig id="viruses-11-00031-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Images of Middle East respiratory syndrome coronavirus (MERS-CoV) S protein-mediated cell–cell fusion. Huh-7 cells were co-cultured with 293T/EGFP cells (<bold>left</bold>) or 293T/MERS/EGFP cells in the presence of PBS (<bold>middle</bold>) or 10 μM HR2P-M2 peptide (<bold>right</bold>) at 37 °C for 2h. The fused cells (one of the fused cell is indicated by an arrow) and the unfused cells were counted under a fluorescence microscope. Scale bars, 200 μm.</p></caption><graphic xlink:href="viruses-11-00031-g001"></graphic></fig><fig id="viruses-11-00031-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Strong synergism of HR2P-M2 combined with m336 against MERS-CoV pseudovirus infection. The effective concentrations for inhibiting MERS-CoV pseudovirus infection are plotted in two curves. The blue curves represent inhibitors used alone, and the red curves represent each inhibitor used in combination. The width between two curves represents the fold of enhancement between an inhibitor used alone and in combination.</p></caption><graphic xlink:href="viruses-11-00031-g002"></graphic></fig><fig id="viruses-11-00031-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Strong synergism resulting from the HR2P-M2/m336 combination against MERS-CoV S protein-mediated cell–cell fusion.</p></caption><graphic xlink:href="viruses-11-00031-g003"></graphic></fig><fig id="viruses-11-00031-f004" orientation="portrait" position="float"><label>Figure 4</label><caption><p>MERS-CoV pseudovirus inhibitory activity as determined from sera of BALB/c mice treated with m336 (0.01 mg) alone, HR2P-M2 (1 mg) alone, or m336 (0.01 mg)/HR2P-M2 (1 mg) in combination. Data are presented as means ± SD. **, and *** represent <italic>p</italic> < 0.01, and <italic>p</italic> < 0.001, respectively.</p></caption><graphic xlink:href="viruses-11-00031-g004"></graphic></fig><table-wrap id="viruses-11-00031-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">viruses-11-00031-t001_Table 1</object-id><label>Table 1</label><caption><p>Combination index (CI) and fold of enhancement for inhibiting MERS-CoV pseudovirus infection by HR2P-M2 (μM) and m336 (nM) tested in combination.</p></caption><table frame="hsides" rules="groups"><thead><tr><th rowspan="3" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" colspan="1">% Inhibition</th><th rowspan="3" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" colspan="1">CI</th><th colspan="3" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">HR2P-M2</th><th colspan="3" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">m336</th></tr><tr><th colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Concentration (μM)</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fold of</th><th colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Concentration (nM)</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fold of</th></tr><tr><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Alone</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">in Mixture</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Enhancement</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Alone</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">in Mixture</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Enhancement</th></tr></thead><tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1">50</td><td align="center" valign="middle" rowspan="1" colspan="1">0.197</td><td align="center" valign="middle" rowspan="1" colspan="1">0.574</td><td align="center" valign="middle" rowspan="1" colspan="1">0.069</td><td align="center" valign="middle" rowspan="1" colspan="1">8.36</td><td align="center" valign="middle" rowspan="1" colspan="1">0.066</td><td align="center" valign="middle" rowspan="1" colspan="1">0.005</td><td align="center" valign="middle" rowspan="1" colspan="1">12.94</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">60</td><td align="center" valign="middle" rowspan="1" colspan="1">0.183</td><td align="center" valign="middle" rowspan="1" colspan="1">0.874</td><td align="center" valign="middle" rowspan="1" colspan="1">0.097</td><td align="center" valign="middle" rowspan="1" colspan="1">9.05</td><td align="center" valign="middle" rowspan="1" colspan="1">0.099</td><td align="center" valign="middle" rowspan="1" colspan="1">0.007</td><td align="center" valign="middle" rowspan="1" colspan="1">13.88</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">70</td><td align="center" valign="middle" rowspan="1" colspan="1">0.168</td><td align="center" valign="middle" rowspan="1" colspan="1">1.381</td><td align="center" valign="middle" rowspan="1" colspan="1">0.140</td><td align="center" valign="middle" rowspan="1" colspan="1">9.87</td><td align="center" valign="middle" rowspan="1" colspan="1">0.155</td><td align="center" valign="middle" rowspan="1" colspan="1">0.010</td><td align="center" valign="middle" rowspan="1" colspan="1">14.98</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">80</td><td align="center" valign="middle" rowspan="1" colspan="1">0.152</td><td align="center" valign="middle" rowspan="1" colspan="1">2.415</td><td align="center" valign="middle" rowspan="1" colspan="1">0.220</td><td align="center" valign="middle" rowspan="1" colspan="1">10.96</td><td align="center" valign="middle" rowspan="1" colspan="1">0.268</td><td align="center" valign="middle" rowspan="1" colspan="1">0.016</td><td align="center" valign="middle" rowspan="1" colspan="1">16.44</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">90</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.131</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5.598</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.436</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">12.85</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.610</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.032</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">18.92</td></tr></tbody></table><table-wrap-foot><fn><p>Note: Each sample was tested in triplicate, and the mean values are presented. Ratio of molar concentration of HR2P-M2 and m336 in combination is 10,000:1.</p></fn></table-wrap-foot></table-wrap><table-wrap id="viruses-11-00031-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">viruses-11-00031-t002_Table 2</object-id><label>Table 2</label><caption><p>Combination index and fold of enhancement for inhibiting MERS-CoV S protein-mediated cell–cell fusion by the HR2P-M2/m336 combination.</p></caption><table frame="hsides" rules="groups"><thead><tr><th rowspan="3" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" colspan="1">% Inhibition</th><th rowspan="3" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" colspan="1">CI</th><th colspan="3" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">HR2P-M2</th><th colspan="3" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">m336</th></tr><tr><th colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Concentration (μM)</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fold of</th><th colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Concentration (nM)</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fold of</th></tr><tr><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Alone</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">in Mixture</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Enhancement</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Alone</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">in Mixture</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Enhancement</th></tr></thead><tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1">50</td><td align="center" valign="middle" rowspan="1" colspan="1">0.271</td><td align="center" valign="middle" rowspan="1" colspan="1">0.511</td><td align="center" valign="middle" rowspan="1" colspan="1">0.110</td><td align="center" valign="middle" rowspan="1" colspan="1">4.64</td><td align="center" valign="middle" rowspan="1" colspan="1">0.440</td><td align="center" valign="middle" rowspan="1" colspan="1">0.024</td><td align="center" valign="middle" rowspan="1" colspan="1">17.96</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">60</td><td align="center" valign="middle" rowspan="1" colspan="1">0.274</td><td align="center" valign="middle" rowspan="1" colspan="1">0.713</td><td align="center" valign="middle" rowspan="1" colspan="1">0.156</td><td align="center" valign="middle" rowspan="1" colspan="1">4.57</td><td align="center" valign="middle" rowspan="1" colspan="1">0.625</td><td align="center" valign="middle" rowspan="1" colspan="1">0.035</td><td align="center" valign="middle" rowspan="1" colspan="1">18.04</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">70</td><td align="center" valign="middle" rowspan="1" colspan="1">0.278</td><td align="center" valign="middle" rowspan="1" colspan="1">1.025</td><td align="center" valign="middle" rowspan="1" colspan="1">0.228</td><td align="center" valign="middle" rowspan="1" colspan="1">4.50</td><td align="center" valign="middle" rowspan="1" colspan="1">0.918</td><td align="center" valign="middle" rowspan="1" colspan="1">0.051</td><td align="center" valign="middle" rowspan="1" colspan="1">18.12</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">80</td><td align="center" valign="middle" rowspan="1" colspan="1">0.282</td><td align="center" valign="middle" rowspan="1" colspan="1">1.596</td><td align="center" valign="middle" rowspan="1" colspan="1">0.362</td><td align="center" valign="middle" rowspan="1" colspan="1">4.41</td><td align="center" valign="middle" rowspan="1" colspan="1">1.466</td><td align="center" valign="middle" rowspan="1" colspan="1">0.080</td><td align="center" valign="middle" rowspan="1" colspan="1">18.22</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">90</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.288</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3.106</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.726</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4.28</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.965</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.161</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">18.38</td></tr></tbody></table><table-wrap-foot><fn><p>Note: Each sample was tested in triplicate, and the mean values are presented. The molar concentration ratio of HR2P-M2 and m336 in combination is 4500:1.</p></fn></table-wrap-foot></table-wrap><table-wrap id="viruses-11-00031-t003" orientation="portrait" position="float"><object-id pub-id-type="pii">viruses-11-00031-t003_Table 3</object-id><label>Table 3</label><caption><p>Sensitivity of MERS-CoV pseudoviruses with or without mutations in the receptor-binding domain (RBD) to the inhibitory activity of m336 (nM) and HR2P-M2 (μM) separately.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">MERS-CoV Pseudovirus</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">IC<sub>50</sub> (nM) of m336</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">RR<sub>50</sub> (Fold of Resistance)</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"><italic>p</italic></th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">IC<sub>50</sub> (μM) of HR2P-M2</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">RR<sub>50</sub> (Fold of Resistance)</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"><italic>p</italic></th></tr></thead><tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1">Wild-type</td><td align="center" valign="middle" rowspan="1" colspan="1">0.055 ± 0.009</td><td align="center" valign="middle" rowspan="1" colspan="1">—</td><td align="center" valign="middle" rowspan="1" colspan="1">—</td><td align="center" valign="middle" rowspan="1" colspan="1">0.553 ± 0.056</td><td align="center" valign="middle" rowspan="1" colspan="1">—</td><td align="center" valign="middle" rowspan="1" colspan="1">—</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">D509G</td><td align="center" valign="middle" rowspan="1" colspan="1">0.116 ± 0.020</td><td align="center" valign="middle" rowspan="1" colspan="1">2.11</td><td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td><td align="center" valign="middle" rowspan="1" colspan="1">0.619 ± 0.079</td><td align="center" valign="middle" rowspan="1" colspan="1">1.12</td><td align="center" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">D510G</td><td align="center" valign="middle" rowspan="1" colspan="1">0.450 ± 0.085</td><td align="center" valign="middle" rowspan="1" colspan="1">8.18</td><td align="center" valign="middle" rowspan="1" colspan="1"><0.05</td><td align="center" valign="middle" rowspan="1" colspan="1">0.679 ± 0.144</td><td align="center" valign="middle" rowspan="1" colspan="1">1.23</td><td align="center" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Q522H</td><td align="center" valign="middle" rowspan="1" colspan="1">0.148 ± 0.051</td><td align="center" valign="middle" rowspan="1" colspan="1">2.69</td><td align="center" valign="middle" rowspan="1" colspan="1"><0.01</td><td align="center" valign="middle" rowspan="1" colspan="1">0.677 ± 0.071</td><td align="center" valign="middle" rowspan="1" colspan="1">1.22</td><td align="center" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I529T</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.215 ± 0.055</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3.91</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><0.01</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.574 ± 0.209</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.04</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">>0.05</td></tr></tbody></table><table-wrap-foot><fn><p>Note: Each sample was tested in triplicate. Data are presented as means ± SD. Resistance ratio (RR<sub>50</sub>) values are based on IC<sub>50</sub> of a mutant strain divided by IC<sub>50</sub> of the wild-type stain. The significance of the difference between a mutant strain and the wild-type strain was statistically analyzed by a two-tailed unpaired Student’s <italic>t</italic>-test using GraphPad Prism, version 5.0. Values with <italic>p</italic> < 0.05 and <italic>p</italic> < 0.01 were considered statistically significant and very significant, respectively.</p></fn></table-wrap-foot></table-wrap><table-wrap id="viruses-11-00031-t004" orientation="portrait" position="float"><object-id pub-id-type="pii">viruses-11-00031-t004_Table 4</object-id><label>Table 4</label><caption><p>Combination index and fold of enhancement for inhibiting MERS-CoV pseudoviruses with or without mutations in RBD in S1 subunit and HR1 in S2 subunit of MERS-CoV S protein by HR2P-M2 and m336.</p></caption><table frame="hsides" rules="groups"><thead><tr><th rowspan="3" align="center" valign="middle" style="border-top:solid thin" colspan="1">% Inhibition</th><th rowspan="3" align="center" valign="middle" style="border-top:solid thin" colspan="1">CI</th><th colspan="3" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">HR2P-M2</th><th colspan="3" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">m336</th></tr><tr><th colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Concentration (μM)</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fold of</th><th colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Concentration (μM)</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fold of</th></tr><tr><th align="center" valign="middle" rowspan="1" colspan="1">Alone</th><th align="center" valign="middle" rowspan="1" colspan="1">in Mixture</th><th align="center" valign="middle" rowspan="1" colspan="1">Enhancement</th><th align="center" valign="middle" rowspan="1" colspan="1">Alone</th><th align="center" valign="middle" rowspan="1" colspan="1">in Mixture</th><th align="center" valign="middle" rowspan="1" colspan="1">Enhancement</th></tr></thead><tbody><tr><td colspan="2" align="center" valign="middle" style="border-top:solid thin" rowspan="1">Wild type</td><td align="center" valign="middle" style="border-top:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-top:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-top:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-top:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-top:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-top:solid thin" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">50</td><td align="center" valign="middle" rowspan="1" colspan="1">0.197</td><td align="center" valign="middle" rowspan="1" colspan="1">0.574</td><td align="center" valign="middle" rowspan="1" colspan="1">0.069</td><td align="center" valign="middle" rowspan="1" colspan="1">8.36</td><td align="center" valign="middle" rowspan="1" colspan="1">0.066</td><td align="center" valign="middle" rowspan="1" colspan="1">0.005</td><td align="center" valign="middle" rowspan="1" colspan="1">12.94</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">60</td><td align="center" valign="middle" rowspan="1" colspan="1">0.183</td><td align="center" valign="middle" rowspan="1" colspan="1">0.874</td><td align="center" valign="middle" rowspan="1" colspan="1">0.097</td><td align="center" valign="middle" rowspan="1" colspan="1">9.05</td><td align="center" valign="middle" rowspan="1" colspan="1">0.099</td><td align="center" valign="middle" rowspan="1" colspan="1">0.007</td><td align="center" valign="middle" rowspan="1" colspan="1">13.88</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">70</td><td align="center" valign="middle" rowspan="1" colspan="1">0.168</td><td align="center" valign="middle" rowspan="1" colspan="1">1.381</td><td align="center" valign="middle" rowspan="1" colspan="1">0.140</td><td align="center" valign="middle" rowspan="1" colspan="1">9.87</td><td align="center" valign="middle" rowspan="1" colspan="1">0.155</td><td align="center" valign="middle" rowspan="1" colspan="1">0.010</td><td align="center" valign="middle" rowspan="1" colspan="1">14.98</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">80</td><td align="center" valign="middle" rowspan="1" colspan="1">0.152</td><td align="center" valign="middle" rowspan="1" colspan="1">2.415</td><td align="center" valign="middle" rowspan="1" colspan="1">0.220</td><td align="center" valign="middle" rowspan="1" colspan="1">10.96</td><td align="center" valign="middle" rowspan="1" colspan="1">0.268</td><td align="center" valign="middle" rowspan="1" colspan="1">0.016</td><td align="center" valign="middle" rowspan="1" colspan="1">16.44</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">90</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.131</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5.598</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.436</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">12.85</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.610</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.032</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">18.92</td></tr><tr><td colspan="2" align="center" valign="middle" rowspan="1">D509G in RBD</td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">50</td><td align="center" valign="middle" rowspan="1" colspan="1">0.296</td><td align="center" valign="middle" rowspan="1" colspan="1">0.912</td><td align="center" valign="middle" rowspan="1" colspan="1">0.155</td><td align="center" valign="middle" rowspan="1" colspan="1">5.88</td><td align="center" valign="middle" rowspan="1" colspan="1">0.273</td><td align="center" valign="middle" rowspan="1" colspan="1">0.034</td><td align="center" valign="middle" rowspan="1" colspan="1">7.91</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">60</td><td align="center" valign="middle" rowspan="1" colspan="1">0.29</td><td align="center" valign="middle" rowspan="1" colspan="1">1.335</td><td align="center" valign="middle" rowspan="1" colspan="1">0.217</td><td align="center" valign="middle" rowspan="1" colspan="1">6.15</td><td align="center" valign="middle" rowspan="1" colspan="1">0.379</td><td align="center" valign="middle" rowspan="1" colspan="1">0.048</td><td align="center" valign="middle" rowspan="1" colspan="1">7.87</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">70</td><td align="center" valign="middle" rowspan="1" colspan="1">0.282</td><td align="center" valign="middle" rowspan="1" colspan="1">2.023</td><td align="center" valign="middle" rowspan="1" colspan="1">0.313</td><td align="center" valign="middle" rowspan="1" colspan="1">6.47</td><td align="center" valign="middle" rowspan="1" colspan="1">0.544</td><td align="center" valign="middle" rowspan="1" colspan="1">0.070</td><td align="center" valign="middle" rowspan="1" colspan="1">7.83</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">80</td><td align="center" valign="middle" rowspan="1" colspan="1">0.274</td><td align="center" valign="middle" rowspan="1" colspan="1">3.358</td><td align="center" valign="middle" rowspan="1" colspan="1">0.489</td><td align="center" valign="middle" rowspan="1" colspan="1">6.87</td><td align="center" valign="middle" rowspan="1" colspan="1">0.844</td><td align="center" valign="middle" rowspan="1" colspan="1">0.109</td><td align="center" valign="middle" rowspan="1" colspan="1">7.77</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">90</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.263</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">7.199</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.956</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">7.53</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.635</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.213</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">7.69</td></tr><tr><td colspan="2" align="center" valign="middle" rowspan="1">D510G in RBD</td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">50</td><td align="center" valign="middle" rowspan="1" colspan="1">0.137</td><td align="center" valign="middle" rowspan="1" colspan="1">0.962</td><td align="center" valign="middle" rowspan="1" colspan="1">0.088</td><td align="center" valign="middle" rowspan="1" colspan="1">10.96</td><td align="center" valign="middle" rowspan="1" colspan="1">0.429</td><td align="center" valign="middle" rowspan="1" colspan="1">0.020</td><td align="center" valign="middle" rowspan="1" colspan="1">21.96</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">60</td><td align="center" valign="middle" rowspan="1" colspan="1">0.145</td><td align="center" valign="middle" rowspan="1" colspan="1">1.523</td><td align="center" valign="middle" rowspan="1" colspan="1">0.153</td><td align="center" valign="middle" rowspan="1" colspan="1">9.96</td><td align="center" valign="middle" rowspan="1" colspan="1">0.763</td><td align="center" valign="middle" rowspan="1" colspan="1">0.034</td><td align="center" valign="middle" rowspan="1" colspan="1">22.43</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">70</td><td align="center" valign="middle" rowspan="1" colspan="1">0.155</td><td align="center" valign="middle" rowspan="1" colspan="1">2.512</td><td align="center" valign="middle" rowspan="1" colspan="1">0.280</td><td align="center" valign="middle" rowspan="1" colspan="1">8.97</td><td align="center" valign="middle" rowspan="1" colspan="1">1.429</td><td align="center" valign="middle" rowspan="1" colspan="1">0.062</td><td align="center" valign="middle" rowspan="1" colspan="1">22.97</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">80</td><td align="center" valign="middle" rowspan="1" colspan="1">0.169</td><td align="center" valign="middle" rowspan="1" colspan="1">4.625</td><td align="center" valign="middle" rowspan="1" colspan="1">0.586</td><td align="center" valign="middle" rowspan="1" colspan="1">7.90</td><td align="center" valign="middle" rowspan="1" colspan="1">3.075</td><td align="center" valign="middle" rowspan="1" colspan="1">0.130</td><td align="center" valign="middle" rowspan="1" colspan="1">23.63</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">90</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.194</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">11.59</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.777</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6.52</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9.74</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.395</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">24.67</td></tr><tr><td colspan="2" align="center" valign="middle" rowspan="1">Q522H in RBD</td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">50</td><td align="center" valign="middle" rowspan="1" colspan="1">0.135</td><td align="center" valign="middle" rowspan="1" colspan="1">0.799</td><td align="center" valign="middle" rowspan="1" colspan="1">0.045</td><td align="center" valign="middle" rowspan="1" colspan="1">17.59</td><td align="center" valign="middle" rowspan="1" colspan="1">0.129</td><td align="center" valign="middle" rowspan="1" colspan="1">0.010</td><td align="center" valign="middle" rowspan="1" colspan="1">12.76</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">60</td><td align="center" valign="middle" rowspan="1" colspan="1">0.143</td><td align="center" valign="middle" rowspan="1" colspan="1">1.243</td><td align="center" valign="middle" rowspan="1" colspan="1">0.067</td><td align="center" valign="middle" rowspan="1" colspan="1">18.67</td><td align="center" valign="middle" rowspan="1" colspan="1">0.166</td><td align="center" valign="middle" rowspan="1" colspan="1">0.015</td><td align="center" valign="middle" rowspan="1" colspan="1">11.21</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">70</td><td align="center" valign="middle" rowspan="1" colspan="1">0.153</td><td align="center" valign="middle" rowspan="1" colspan="1">2.012</td><td align="center" valign="middle" rowspan="1" colspan="1">0.101</td><td align="center" valign="middle" rowspan="1" colspan="1">19.93</td><td align="center" valign="middle" rowspan="1" colspan="1">0.219</td><td align="center" valign="middle" rowspan="1" colspan="1">0.022</td><td align="center" valign="middle" rowspan="1" colspan="1">9.74</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">80</td><td align="center" valign="middle" rowspan="1" colspan="1">0.168</td><td align="center" valign="middle" rowspan="1" colspan="1">3.619</td><td align="center" valign="middle" rowspan="1" colspan="1">0.168</td><td align="center" valign="middle" rowspan="1" colspan="1">21.57</td><td align="center" valign="middle" rowspan="1" colspan="1">0.306</td><td align="center" valign="middle" rowspan="1" colspan="1">0.037</td><td align="center" valign="middle" rowspan="1" colspan="1">8.21</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">90</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.199</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8.757</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.36</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">24.30</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.508</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.08</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6.34</td></tr><tr><td colspan="2" align="center" valign="middle" rowspan="1">I529T in RBD</td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">50</td><td align="center" valign="middle" rowspan="1" colspan="1">0.256</td><td align="center" valign="middle" rowspan="1" colspan="1">0.864</td><td align="center" valign="middle" rowspan="1" colspan="1">0.098</td><td align="center" valign="middle" rowspan="1" colspan="1">8.81</td><td align="center" valign="middle" rowspan="1" colspan="1">0.153</td><td align="center" valign="middle" rowspan="1" colspan="1">0.022</td><td align="center" valign="middle" rowspan="1" colspan="1">7.03</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">60</td><td align="center" valign="middle" rowspan="1" colspan="1">0.242</td><td align="center" valign="middle" rowspan="1" colspan="1">1.295</td><td align="center" valign="middle" rowspan="1" colspan="1">0.139</td><td align="center" valign="middle" rowspan="1" colspan="1">9.32</td><td align="center" valign="middle" rowspan="1" colspan="1">0.23</td><td align="center" valign="middle" rowspan="1" colspan="1">0.031</td><td align="center" valign="middle" rowspan="1" colspan="1">7.45</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">70</td><td align="center" valign="middle" rowspan="1" colspan="1">0.227</td><td align="center" valign="middle" rowspan="1" colspan="1">2.013</td><td align="center" valign="middle" rowspan="1" colspan="1">0.203</td><td align="center" valign="middle" rowspan="1" colspan="1">9.90</td><td align="center" valign="middle" rowspan="1" colspan="1">0.358</td><td align="center" valign="middle" rowspan="1" colspan="1">0.045</td><td align="center" valign="middle" rowspan="1" colspan="1">7.92</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">80</td><td align="center" valign="middle" rowspan="1" colspan="1">0.211</td><td align="center" valign="middle" rowspan="1" colspan="1">3.449</td><td align="center" valign="middle" rowspan="1" colspan="1">0.323</td><td align="center" valign="middle" rowspan="1" colspan="1">10.67</td><td align="center" valign="middle" rowspan="1" colspan="1">0.614</td><td align="center" valign="middle" rowspan="1" colspan="1">0.072</td><td align="center" valign="middle" rowspan="1" colspan="1">8.55</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">90</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.188</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">7.752</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.649</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">11.94</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.383</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.144</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9.58</td></tr><tr><td colspan="2" align="center" valign="middle" rowspan="1">Q1020H in HR1</td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">50</td><td align="center" valign="middle" rowspan="1" colspan="1">0.186</td><td align="center" valign="middle" rowspan="1" colspan="1">0.762</td><td align="center" valign="middle" rowspan="1" colspan="1">0.086</td><td align="center" valign="middle" rowspan="1" colspan="1">8.83</td><td align="center" valign="middle" rowspan="1" colspan="1">0.088</td><td align="center" valign="middle" rowspan="1" colspan="1">0.006</td><td align="center" valign="middle" rowspan="1" colspan="1">13.82</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">60</td><td align="center" valign="middle" rowspan="1" colspan="1">0.189</td><td align="center" valign="middle" rowspan="1" colspan="1">0.954</td><td align="center" valign="middle" rowspan="1" colspan="1">0.106</td><td align="center" valign="middle" rowspan="1" colspan="1">9.04</td><td align="center" valign="middle" rowspan="1" colspan="1">0.100</td><td align="center" valign="middle" rowspan="1" colspan="1">0.008</td><td align="center" valign="middle" rowspan="1" colspan="1">12.84</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">70</td><td align="center" valign="middle" rowspan="1" colspan="1">0.192</td><td align="center" valign="middle" rowspan="1" colspan="1">1.218</td><td align="center" valign="middle" rowspan="1" colspan="1">0.131</td><td align="center" valign="middle" rowspan="1" colspan="1">9.27</td><td align="center" valign="middle" rowspan="1" colspan="1">0.115</td><td align="center" valign="middle" rowspan="1" colspan="1">0.010</td><td align="center" valign="middle" rowspan="1" colspan="1">11.85</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">80</td><td align="center" valign="middle" rowspan="1" colspan="1">0.198</td><td align="center" valign="middle" rowspan="1" colspan="1">1.642</td><td align="center" valign="middle" rowspan="1" colspan="1">0.172</td><td align="center" valign="middle" rowspan="1" colspan="1">9.56</td><td align="center" valign="middle" rowspan="1" colspan="1">0.137</td><td align="center" valign="middle" rowspan="1" colspan="1">0.013</td><td align="center" valign="middle" rowspan="1" colspan="1">10.74</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">90</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.208</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.571</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.257</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">10.01</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.176</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.019</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9.27</td></tr><tr><td colspan="2" align="center" valign="middle" rowspan="1">Q1020R in HR1</td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">50</td><td align="center" valign="middle" rowspan="1" colspan="1">0.293</td><td align="center" valign="middle" rowspan="1" colspan="1">0.69</td><td align="center" valign="middle" rowspan="1" colspan="1">0.119</td><td align="center" valign="middle" rowspan="1" colspan="1">5.79</td><td align="center" valign="middle" rowspan="1" colspan="1">0.073</td><td align="center" valign="middle" rowspan="1" colspan="1">0.009</td><td align="center" valign="middle" rowspan="1" colspan="1">8.30</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">60</td><td align="center" valign="middle" rowspan="1" colspan="1">0.28</td><td align="center" valign="middle" rowspan="1" colspan="1">0.905</td><td align="center" valign="middle" rowspan="1" colspan="1">0.143</td><td align="center" valign="middle" rowspan="1" colspan="1">6.32</td><td align="center" valign="middle" rowspan="1" colspan="1">0.087</td><td align="center" valign="middle" rowspan="1" colspan="1">0.011</td><td align="center" valign="middle" rowspan="1" colspan="1">8.19</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">70</td><td align="center" valign="middle" rowspan="1" colspan="1">0.268</td><td align="center" valign="middle" rowspan="1" colspan="1">1.216</td><td align="center" valign="middle" rowspan="1" colspan="1">0.175</td><td align="center" valign="middle" rowspan="1" colspan="1">6.95</td><td align="center" valign="middle" rowspan="1" colspan="1">0.104</td><td align="center" valign="middle" rowspan="1" colspan="1">0.013</td><td align="center" valign="middle" rowspan="1" colspan="1">8.06</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">80</td><td align="center" valign="middle" rowspan="1" colspan="1">0.254</td><td align="center" valign="middle" rowspan="1" colspan="1">1.743</td><td align="center" valign="middle" rowspan="1" colspan="1">0.223</td><td align="center" valign="middle" rowspan="1" colspan="1">7.80</td><td align="center" valign="middle" rowspan="1" colspan="1">0.131</td><td align="center" valign="middle" rowspan="1" colspan="1">0.017</td><td align="center" valign="middle" rowspan="1" colspan="1">7.92</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">90</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.238</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.997</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.323</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9.29</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.184</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.024</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">7.70</td></tr></tbody></table><table-wrap-foot><fn><p>Note: The molar concentration ratio of HR2P-M2 and m336 in combination against wildtype virus, viruses with mutations in RBD, and those in HR1 is 10,000:1, 4500:1, and 10,000:1, respectively.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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