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Bioessays ; 42(10): e2000091, 2020 10.
Article in English | MEDLINE | ID: covidwho-720302


Despite claims from prominent scientists that SARS-CoV-2 indubitably emerged naturally, the etiology of this novel coronavirus remains a pressing and open question: Without knowing the true nature of a disease, it is impossible for clinicians to appropriately shape their care, for policy-makers to correctly gauge the nature and extent of the threat, and for the public to appropriately modify their behavior. Unless the intermediate host necessary for completing a natural zoonotic jump is identified, the dual-use gain-of-function research practice of viral serial passage should be considered a viable route by which the novel coronavirus arose. The practice of serial passage mimics a natural zoonotic jump, and offers explanations for SARS-CoV-2's distinctive spike-protein region and its unexpectedly high affinity for angiotensin converting enzyme (ACE2), as well as the notable polybasic furin cleavage site within it. Additional molecular clues raise further questions, all of which warrant full investigation into the novel coronavirus's origins and a re-examination of the risks and rewards of dual-use gain-of-function research.

Betacoronavirus/genetics , Coronavirus Infections/etiology , Coronavirus Infections/transmission , Pneumonia, Viral/etiology , Pneumonia, Viral/transmission , Zoonoses/transmission , Amino Acid Sequence , Animals , Betacoronavirus/growth & development , Gain of Function Mutation/genetics , Humans , Pandemics , Peptidyl-Dipeptidase A/metabolism , Protein Binding , Serial Passage , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Zoonoses/virology
Med Sci (Paris) ; 36(8-9): 783-796, 2020.
Article in French | MEDLINE | ID: covidwho-706965


SARS-CoV-2 is a new human coronavirus (CoV), which emerged in People's Republic of China at the end of 2019 and is responsible for the global Covid-19 pandemic that caused more than 540 000 deaths in six months. Understanding the origin of this virus is an important issue and it is necessary to determine the mechanisms of its dissemination in order to be able to contain new epidemics. Based on phylogenetic inferences, sequence analysis and structure-function relationships of coronavirus proteins, informed by the knowledge currently available, we discuss the different scenarios evoked to account for the origin - natural or synthetic - of the virus. On the basis of currently available data, it is impossible to determine whether SARS-CoV-2 is the result of a natural zoonotic emergence or an accidental escape from experimental strains. Regardless of its origin, the study of the evolution of the molecular mechanisms involved in the emergence of this pandemic virus is essential to develop therapeutic and vaccine strategies.

Betacoronavirus/genetics , Communicable Diseases, Emerging/virology , Coronavirus Infections/virology , Coronavirus/classification , Evolution, Molecular , Pandemics , Phylogeny , Pneumonia, Viral/virology , RNA, Viral/genetics , Amino Acid Sequence , Animals , Betacoronavirus/classification , Betacoronavirus/isolation & purification , Biohazard Release , China/epidemiology , Coronaviridae Infections/transmission , Coronaviridae Infections/veterinary , Coronaviridae Infections/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Disease Reservoirs , Gain of Function Mutation , Genome, Viral , HIV/genetics , Host Specificity , Humans , Mammals/virology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Reassortant Viruses/genetics , Sequence Alignment , Sequence Homology, Amino Acid , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/physiology , Zoonoses
mBio ; 11(4)2020 08 07.
Article in English | MEDLINE | ID: covidwho-705638


Proponents of the use of gain-of-function (GOF) experiments with pathogens with pandemic potential (PPP) have argued that such experiments are necessary because they reveal important facets of pathogenesis and can be performed safely. Opponents of GOF experiments with PPP have argued that the risks outweigh the knowledge gained. The COVID-19 pandemic demonstrates the vulnerability of human societies to a new PPP, while also validating some arguments of both camps, questioning others, and suggesting the need to rethink how we approach this class of experiments.

Betacoronavirus/genetics , Coronavirus Infections/virology , Gain of Function Mutation , Pneumonia, Viral/virology , Biomedical Research/ethics , Biomedical Research/standards , Bioterrorism , Containment of Biohazards/ethics , Containment of Biohazards/standards , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Humans , Influenza A Virus, H5N1 Subtype/genetics , Influenza, Human/epidemiology , Influenza, Human/virology , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control