While it is now possible to identify and genetically fingerprint the causative agents of emerging viral diseases, often with extraordinary speed, suitable therapies cannot be developed with equivalent speed, because drug discovery requires information that goes beyond knowledge of the viral genome. Peptides, however, may represent a special opportunity. For all enveloped viruses, fusion between the viral and the target cell membrane is an obligatory step of the life cycle. Class I fusion proteins harbor regions with a repeating pattern of amino acids, the heptad repeats (HRs), that play a key role in fusion, and HR‐derived peptides such as enfuvirtide, in clinical use for HIV, can block the process. Because of their characteristic sequence pattern, HRs are easily identified in the genome by means of computer programs, providing the sequence of candidate peptide inhibitors directly from genomic information. Moreover, a simple chemical modification, the attachment of a cholesterol group, can dramatically increase the antiviral potency of HR‐derived inhibitors and simultaneously improve their pharmacokinetics. Further enhancement can be provided by dimerization of the cholesterol‐conjugated peptide. The examples reported so far include inhibitors of retroviruses, paramyxoviruses, orthomyxoviruses, henipaviruses, coronaviruses, and filoviruses. For some of these viruses, in vivo efficacy has been demonstrated in suitable animal models. The combination of bioinformatic lead identification and potency/pharmacokinetics improvement provided by cholesterol conjugation may form the basis for a rapid response strategy, where development of an emergency cholesterol‐conjugated therapeutic would immediately follow the availability of the genetic information of a new enveloped virus. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

Peptides may represent a special opportunity against emerging viral diseases. Peptides derived from the viral fusion proteins, which can interfere with virus entry into the host cell, can be identified directly from genomic information. When conjugated with cholesterol, their potency is dramatically increased and pharmacokinetics simultaneously improved. Further enhancement is provided by dimerization. Cholesterol conjugation may form the basis for a rapid response strategy, where an emergency therapy would be developed based on genomic information of a new enveloped virus.

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   |texte=   Cholesterol‐conjugated peptide antivirals: a path to a rapid response to emerging viral diseases
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