Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2'-O-ribose methyltransferase.
Identifieur interne : 000185 ( 2020/Analysis ); précédent : 000184; suivant : 000186Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2'-O-ribose methyltransferase.
Auteurs : Rameez Jabeer Khan [Inde] ; Rajat Kumar Jha [Inde] ; Gizachew Muluneh Amera [Inde] ; Monika Jain [Inde] ; Ekampreet Singh [Inde] ; Amita Pathak [Inde] ; Rashmi Prabha Singh [Inde] ; Jayaraman Muthukumaran [Inde] ; Amit Kumar Singh [Inde]Source :
- Journal of biomolecular structure & dynamics [ 1538-0254 ] ; 2020.
Abstract
The recent pandemic associated with SARS-CoV-2, a virus of the Coronaviridae family, has resulted in an unprecedented number of infected people. The highly contagious nature of this virus makes it imperative for us to identify promising inhibitors from pre-existing antiviral drugs. Two druggable targets, namely 3C-like proteinase (3CLpro) and 2'-O-ribose methyltransferase (2'-O-MTase) were selected in this study due to their indispensable nature in the viral life cycle. 3CLpro is a cysteine protease responsible for the proteolysis of replicase polyproteins resulting in the formation of various functional proteins, whereas 2'-O-MTase methylates the ribose 2'-O position of the first and second nucleotide of viral mRNA, which sequesters it from the host immune system. The selected drug target proteins were screened against an in-house library of 123 antiviral drugs. Two promising drug molecules were identified for each protein based on their estimated free energy of binding (ΔG), the orientation of drug molecules in the active site and the interacting residues. The selected protein-drug complexes were then subjected to MD simulation, which consists of various structural parameters to equivalently reflect their physiological state. From the virtual screening results, two drug molecules were selected for each drug target protein [Paritaprevir (ΔG = -9.8 kcal/mol) & Raltegravir (ΔG = -7.8 kcal/mol) for 3CLpro and Dolutegravir (ΔG = -9.4 kcal/mol) and Bictegravir (ΔG = -8.4 kcal/mol) for 2'-OMTase]. After the extensive computational analysis, we proposed that Raltegravir, Paritaprevir, Bictegravir and Dolutegravir are excellent lead candidates for these crucial proteins and they could become potential therapeutic drugs against SARS-CoV-2. Communicated by Ramaswamy H. Sarma.
DOI: 10.1080/07391102.2020.1753577
PubMed: 32266873
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000295
- to stream PubMed, to step Curation: 000295
- to stream PubMed, to step Checkpoint: 000153
- to stream Ncbi, to step Merge: 003812
- to stream Ncbi, to step Curation: 003812
- to stream Ncbi, to step Checkpoint: 003812
- to stream Main, to step Merge: 000185
- to stream Main, to step Curation: 000185
- to stream Main, to step Exploration: 000185
- to stream 2020, to step Extraction: 000185
Links to Exploration step
pubmed:32266873Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2'-O-ribose methyltransferase.</title>
<author><name sortKey="Khan, Rameez Jabeer" sort="Khan, Rameez Jabeer" uniqKey="Khan R" first="Rameez Jabeer" last="Khan">Rameez Jabeer Khan</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jha, Rajat Kumar" sort="Jha, Rajat Kumar" uniqKey="Jha R" first="Rajat Kumar" last="Jha">Rajat Kumar Jha</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Amera, Gizachew Muluneh" sort="Amera, Gizachew Muluneh" uniqKey="Amera G" first="Gizachew Muluneh" last="Amera">Gizachew Muluneh Amera</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jain, Monika" sort="Jain, Monika" uniqKey="Jain M" first="Monika" last="Jain">Monika Jain</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Singh, Ekampreet" sort="Singh, Ekampreet" uniqKey="Singh E" first="Ekampreet" last="Singh">Ekampreet Singh</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pathak, Amita" sort="Pathak, Amita" uniqKey="Pathak A" first="Amita" last="Pathak">Amita Pathak</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Chemistry, Indian Institute of Technology, New Delhi, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Chemistry, Indian Institute of Technology, New Delhi</wicri:regionArea>
<wicri:noRegion>New Delhi</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Singh, Rashmi Prabha" sort="Singh, Rashmi Prabha" uniqKey="Singh R" first="Rashmi Prabha" last="Singh">Rashmi Prabha Singh</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, IILM College of Engineering & Technology, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, IILM College of Engineering & Technology, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Muthukumaran, Jayaraman" sort="Muthukumaran, Jayaraman" uniqKey="Muthukumaran J" first="Jayaraman" last="Muthukumaran">Jayaraman Muthukumaran</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Singh, Amit Kumar" sort="Singh, Amit Kumar" uniqKey="Singh A" first="Amit Kumar" last="Singh">Amit Kumar Singh</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2020">2020</date>
<idno type="RBID">pubmed:32266873</idno>
<idno type="pmid">32266873</idno>
<idno type="doi">10.1080/07391102.2020.1753577</idno>
<idno type="wicri:Area/PubMed/Corpus">000295</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000295</idno>
<idno type="wicri:Area/PubMed/Curation">000295</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000295</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000153</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000153</idno>
<idno type="wicri:Area/Ncbi/Merge">003812</idno>
<idno type="wicri:Area/Ncbi/Curation">003812</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">003812</idno>
<idno type="wicri:Area/Main/Merge">000185</idno>
<idno type="wicri:Area/Main/Curation">000185</idno>
<idno type="wicri:Area/Main/Exploration">000185</idno>
<idno type="wicri:Area/2020/Extraction">000185</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2'-O-ribose methyltransferase.</title>
<author><name sortKey="Khan, Rameez Jabeer" sort="Khan, Rameez Jabeer" uniqKey="Khan R" first="Rameez Jabeer" last="Khan">Rameez Jabeer Khan</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jha, Rajat Kumar" sort="Jha, Rajat Kumar" uniqKey="Jha R" first="Rajat Kumar" last="Jha">Rajat Kumar Jha</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Amera, Gizachew Muluneh" sort="Amera, Gizachew Muluneh" uniqKey="Amera G" first="Gizachew Muluneh" last="Amera">Gizachew Muluneh Amera</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jain, Monika" sort="Jain, Monika" uniqKey="Jain M" first="Monika" last="Jain">Monika Jain</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Singh, Ekampreet" sort="Singh, Ekampreet" uniqKey="Singh E" first="Ekampreet" last="Singh">Ekampreet Singh</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pathak, Amita" sort="Pathak, Amita" uniqKey="Pathak A" first="Amita" last="Pathak">Amita Pathak</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Chemistry, Indian Institute of Technology, New Delhi, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Chemistry, Indian Institute of Technology, New Delhi</wicri:regionArea>
<wicri:noRegion>New Delhi</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Singh, Rashmi Prabha" sort="Singh, Rashmi Prabha" uniqKey="Singh R" first="Rashmi Prabha" last="Singh">Rashmi Prabha Singh</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, IILM College of Engineering & Technology, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, IILM College of Engineering & Technology, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Muthukumaran, Jayaraman" sort="Muthukumaran, Jayaraman" uniqKey="Muthukumaran J" first="Jayaraman" last="Muthukumaran">Jayaraman Muthukumaran</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Singh, Amit Kumar" sort="Singh, Amit Kumar" uniqKey="Singh A" first="Amit Kumar" last="Singh">Amit Kumar Singh</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, U.P</wicri:regionArea>
<wicri:noRegion>U.P</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of biomolecular structure & dynamics</title>
<idno type="eISSN">1538-0254</idno>
<imprint><date when="2020" type="published">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The recent pandemic associated with SARS-CoV-2, a virus of the Coronaviridae family, has resulted in an unprecedented number of infected people. The highly contagious nature of this virus makes it imperative for us to identify promising inhibitors from pre-existing antiviral drugs. Two druggable targets, namely 3C-like proteinase (3CLpro) and 2'-O-ribose methyltransferase (2'-O-MTase) were selected in this study due to their indispensable nature in the viral life cycle. 3CLpro is a cysteine protease responsible for the proteolysis of replicase polyproteins resulting in the formation of various functional proteins, whereas 2'-O-MTase methylates the ribose 2'-O position of the first and second nucleotide of viral mRNA, which sequesters it from the host immune system. The selected drug target proteins were screened against an in-house library of 123 antiviral drugs. Two promising drug molecules were identified for each protein based on their estimated free energy of binding (ΔG), the orientation of drug molecules in the active site and the interacting residues. The selected protein-drug complexes were then subjected to MD simulation, which consists of various structural parameters to equivalently reflect their physiological state. From the virtual screening results, two drug molecules were selected for each drug target protein [Paritaprevir (ΔG = -9.8 kcal/mol) & Raltegravir (ΔG = -7.8 kcal/mol) for 3CLpro and Dolutegravir (ΔG = -9.4 kcal/mol) and Bictegravir (ΔG = -8.4 kcal/mol) for 2'-OMTase]. After the extensive computational analysis, we proposed that Raltegravir, Paritaprevir, Bictegravir and Dolutegravir are excellent lead candidates for these crucial proteins and they could become potential therapeutic drugs against SARS-CoV-2. Communicated by Ramaswamy H. Sarma.</div>
</front>
</TEI>
<affiliations><list><country><li>Inde</li>
</country>
</list>
<tree><country name="Inde"><noRegion><name sortKey="Khan, Rameez Jabeer" sort="Khan, Rameez Jabeer" uniqKey="Khan R" first="Rameez Jabeer" last="Khan">Rameez Jabeer Khan</name>
</noRegion>
<name sortKey="Amera, Gizachew Muluneh" sort="Amera, Gizachew Muluneh" uniqKey="Amera G" first="Gizachew Muluneh" last="Amera">Gizachew Muluneh Amera</name>
<name sortKey="Jain, Monika" sort="Jain, Monika" uniqKey="Jain M" first="Monika" last="Jain">Monika Jain</name>
<name sortKey="Jha, Rajat Kumar" sort="Jha, Rajat Kumar" uniqKey="Jha R" first="Rajat Kumar" last="Jha">Rajat Kumar Jha</name>
<name sortKey="Muthukumaran, Jayaraman" sort="Muthukumaran, Jayaraman" uniqKey="Muthukumaran J" first="Jayaraman" last="Muthukumaran">Jayaraman Muthukumaran</name>
<name sortKey="Pathak, Amita" sort="Pathak, Amita" uniqKey="Pathak A" first="Amita" last="Pathak">Amita Pathak</name>
<name sortKey="Singh, Amit Kumar" sort="Singh, Amit Kumar" uniqKey="Singh A" first="Amit Kumar" last="Singh">Amit Kumar Singh</name>
<name sortKey="Singh, Ekampreet" sort="Singh, Ekampreet" uniqKey="Singh E" first="Ekampreet" last="Singh">Ekampreet Singh</name>
<name sortKey="Singh, Rashmi Prabha" sort="Singh, Rashmi Prabha" uniqKey="Singh R" first="Rashmi Prabha" last="Singh">Rashmi Prabha Singh</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/2020/Analysis
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000185 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/2020/Analysis/biblio.hfd -nk 000185 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= 2020 |étape= Analysis |type= RBID |clé= pubmed:32266873 |texte= Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2'-O-ribose methyltransferase. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/2020/Analysis/RBID.i -Sk "pubmed:32266873" \ | HfdSelect -Kh $EXPLOR_AREA/Data/2020/Analysis/biblio.hfd \ | NlmPubMed2Wicri -a SrasV1
This area was generated with Dilib version V0.6.33. |