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Gain-of-function and origin of Covid19
1Universiy of Paris Cité, Paris, France.
Presse Medicale (Paris, France : 1983)
|June 3, 2023
Summary
The origin of SARS-CoV-2 remains uncertain, with two main theories: natural zoonotic spillover or a laboratory accident involving gain-of-function research on viruses. Understanding its emergence is crucial for pandemic preparedness.
Area of Science:
- Virology
- Epidemiology
- Genetics
Background:
- Wild viruses circulating in animal reservoirs pose a risk of zoonotic transmission to humans.
- Genetic manipulation of viruses, particularly those with pandemic potential like influenza and coronaviruses, has been explored to understand pathogenicity.
- Gain-of-function research on dangerous pathogens was subject to a moratorium in the US from 2014-2017.
Purpose of the Study:
- To review the current understanding and ongoing mystery surrounding the origin of SARS-CoV-2, the virus responsible for COVID-19.
- To analyze the genetic characteristics of SARS-CoV-2, including its highly contagious nature and unique furin cleavage site.
- To present and evaluate the two primary hypotheses for SARS-CoV-2 emergence: natural zoonotic origin versus laboratory-related incident.
Main Methods:
- Review of scientific literature and epidemiological data related to SARS-CoV-2 emergence.
- Analysis of the genetic makeup of SARS-CoV-2, comparing it to related coronaviruses and known viral reservoirs.
- Evaluation of the plausibility of natural spillover versus laboratory-based scenarios, considering geographical and genetic evidence.
Main Results:
- SARS-CoV-2 emerged in Wuhan, China, in late 2019, exhibiting high contagiousness and genetic homogeneity in initial isolates.
- A unique furin cleavage site in the Spike protein, a key virulence factor, is present in SARS-CoV-2 but absent in related sarbecoviruses.
- No intermediate host has been identified for SARS-CoV-2, unlike previous SARS and MERS outbreaks, and initial spread was confined to Wuhan.
Conclusions:
- The origin of SARS-CoV-2 is still debated, with significant questions remaining about its emergence.
- The natural origin hypothesis faces challenges in explaining the Wuhan epicenter and the virus's specific genetic features, such as the furin site.
- The laboratory accident hypothesis, involving gain-of-function research or accidental human infection with a lab-grown virus, remains a plausible alternative requiring further investigation.
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