COVID-19: Time to exonerate the pangolin from the transmission of SARS-CoV-2 to humans

Frutos, Roger; Serra‐Cobo, Jordi; Chen, Tianmu; Devaux, Christian

doi:10.1016/j.meegid.2020.104493

Cited by 84 publications

(102 citation statements)

References 63 publications

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“…The hypothesis of pangolin ( M. javanica ) as an intermediate host for SARS-CoV-2 quickly became mainstream ( 32 , 44 ). We recently demonstrated that pangolin is unlikely to be the intermediate host and that transmission to humans could just as easily have taken place via another animal ( 33 ).…”

Section: Resultsmentioning

confidence: 99%

“…The snake hypothesis was quickly ruled out ( 32 ). Although the pangolin hypothesis was the mainstream, it was also recently excluded ( 33 , 34 ). At the same time, other species were singled out.…”

Section: Introductionmentioning

confidence: 99%

“…The analysis of electrostatic potential surface generation of ACE2 variants highlight minor differences in surface charges for mouse and frog sequence insertions compatible with lower susceptibility of these species to SARS-CoV-2. Finally, the broad spectrum of potentially susceptible species argues in favor of the circulation model ( 33 ) rather than in favor of the spillover model ( 39 ).…”

Section: Introductionmentioning

confidence: 99%

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Can ACE2 Receptor Polymorphism Predict Species Susceptibility to SARS-CoV-2?

Devaux

Pinault

Osman

et al. 2021

Front. Public Health

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A novel severe acute respiratory syndrome coronavirus, SARS-CoV-2, emerged in China in December 2019 and spread worldwide, causing more than 1.3 million deaths in 11 months. Similar to the human SARS-CoV, SARS-CoV-2 shares strong sequence homologies with a sarbecovirus circulating in Rhinolophus affinis bats. Because bats are expected to be able to transmit their coronaviruses to intermediate animal hosts that in turn are a source of viruses able to cross species barriers and infect humans (so-called spillover model), the identification of an intermediate animal reservoir was the subject of intense researches. It was claimed that a reptile (Ophiophagus hannah) was the intermediate host. This hypothesis was quickly ruled out and replaced by the pangolin (Manis javanica) hypothesis. Yet, pangolin was also recently exonerated from SARS-CoV-2 transmission to humans, leaving other animal species as presumed guilty. Guided by the spillover model, several laboratories investigated in silico the species polymorphism of the angiotensin I converting enzyme 2 (ACE2) to find the best fits with the SARS-CoV-2 spike receptor-binding site. Following the same strategy, we used multi-sequence alignment, 3-D structure analysis, and electrostatic potential surface generation of ACE2 variants to predict their binding capacity to SARS-CoV-2. We report evidence that such simple in silico investigation is a powerful tool to quickly screen which species are potentially susceptible to SARS-CoV-2. However, possible receptor binding does not necessarily lead to successful replication in host. Therefore, we also discuss here the limitations of these in silico approaches in our quest on the origins of COVID-19 pandemic.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Can ACE2 Receptor Polymorphism Predict Species Susceptibility to SARS-CoV-2?

Devaux

Pinault

Osman

et al. 2021

Front. Public Health

Self Cite

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“…They should rather be compared on the basis of their respective likelihood, but these would currently be very difficult to estimate, in the absence of key information, in particular on the precise experiments performed in China on closely related viruses before the pandemic. Besides, the pangolin hypothesis has now been strongly questioned (Lee et al 2020 ; Choo et al 2020 ; Frutos et al 2020 ). Regarding the hypothesis of reverse engineering, even though it is not obvious to identify any trace a posteriori there are currently several traceless options for genetic engineering.…”

Section: Current Status: the Jury Is Still Outmentioning

confidence: 99%

Tracing the origins of SARS-COV-2 in coronavirus phylogenies: a review

et al. 2021

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SARS-CoV-2 is a new human coronavirus (CoV), which emerged in China in late 2019 and is responsible for the global COVID-19 pandemic that caused more than 97 million infections and 2 million deaths in 12 months. Understanding the origin of this virus is an important issue, and it is necessary to determine the mechanisms of viral dissemination in order to contain future epidemics. Based on phylogenetic inferences, sequence analysis and structure–function relationships of coronavirus proteins, informed by the knowledge currently available on the virus, we discuss the different scenarios on the origin—natural or synthetic—of the virus. The data currently available are not sufficient to firmly assert whether SARS-CoV2 results from a zoonotic emergence or from an accidental escape of a laboratory strain. This question needs to be solved because it has important consequences on the risk/benefit balance of our interactions with ecosystems, on intensive breeding of wild and domestic animals, on some laboratory practices and on scientific policy and biosafety regulations. Regardless of COVID-19 origin, studying the evolution of the molecular mechanisms involved in the emergence of pandemic viruses is essential to develop therapeutic and vaccine strategies and to prevent future zoonoses. This article is a translation and update of a French article published in Médecine/Sciences, August/September 2020 (10.1051/medsci/2020123).

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“…There is a unique feature of SARS-CoV-2 S protein which possesses a polybasic furin cleavage site at the junction of S1 and S2 subunits. This feature is believed to have emerged during viral transmission from zoonotic host to human 25–27 , and is key to SARS-CoV-2 high transmissibility in humans 28,29 . Although robust SARS-CoV-2 infection of human lungs requires a multibasic cleavage site 30 , interestingly, both cleaved and uncleaved versions of S protein co-exist on virions purified from viral culture on Vero cells 31,32 .…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates

Kalnin

Plitnik²,

Kishko

et al. 2020

Preprint

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An effective vaccine to address the global pandemic of coronavirus disease 2019 (COVID-19) is an urgent public health priority. Novel synthetic mRNA and vector-based vaccine technologies offer an expeditious development path alternative to traditional vaccine approaches. Here we describe the efforts to utilize an mRNA platform for rational design and evaluations of mRNA vaccine candidates based on Spike (S) glycoprotein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Several mRNA constructs expressing various structural conformations of S-protein, including wild type (WT), a pre-fusion stabilized mutant (2P), a furin cleavage-site mutant (GSAS) and a double mutant form (2P/GSAS), were tested in a preclinical animal model for their capacity to elicit neutralizing antibodies (nAbs). The lead 2P/GSAS candidate was further assessed in dose-ranging studies in mice and Cynomolgus macaques. The selected 2P/GSAS vaccine formulation, now designated MRT5500, elicited potent nAbs as measured in two types of neutralization assays. In addition, MRT5500 elicited TH1-biased responses in both mouse and non-human primate species, a result that helps to address a hypothetical concern regarding potential vaccine-associated enhanced respiratory diseases associated with TH2-biased responses. These data position MRT5500 as a viable vaccine candidate for clinical development against COVID-19.

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COVID-19: Time to exonerate the pangolin from the transmission of SARS-CoV-2 to humans

Cited by 84 publications

References 63 publications

Can ACE2 Receptor Polymorphism Predict Species Susceptibility to SARS-CoV-2?

Can ACE2 Receptor Polymorphism Predict Species Susceptibility to SARS-CoV-2?

Tracing the origins of SARS-COV-2 in coronavirus phylogenies: a review

Immunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates

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