• Corpus ID: 231847017

An open debate on SARS-CoV-2's proximal origin is long overdue

  title={An open debate on SARS-CoV-2's proximal origin is long overdue},
  author={Rossana Segreto and Yuri Deigin and K. McCairn and Alejandro Sousa and Dan Sirotkin and Karl Sirotkin and Jonathan J. Couey and Adrian Jones and Daoyu Zhang Department of Microbiology and University of Innsbruck and Austria and Youthereum Genetics Inc. and Toronto and Ontario and Canada. and Synaptek - Deep Learning Solutions and G{\^i}fu and Japan. and R Monforte and Lugo and Spain. and University of Santiago de Compostela and Karl Sirotkin Llc and Lake Mary and FL 32746 and Usa and University of Pittsburgh and School of Clinical Medicine and Independent Researcher and Independent Researcher},
There is a near consensus view that SARS-CoV-2 has a natural zoonotic origin;however, several characteristics of SARS-CoV-2 taken together are not easily explained by a natural zoonotic origin hypothesis. These include: a low rate of evolution in the early phase of transmission;the lack of evidence of recombination events;a high pre-existing binding to human ACE2;a novel furin cleavage site insert;a flat glycan binding domain of the spike protein which conflicts with host evasion survival… 

Figures from this paper



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

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.

No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2

This work formally test whether any of the recurrent mutations that have been observed in SARS-CoV-2 are significantly associated with increased viral transmission, and develops a phylogenetic index to quantify the relative number of descendants in sister clades with and without a specific allele.

The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor

Molecular dynamics simulations reveal a temporal dimension of coronaviruses interactions with the host receptor, exposing an exceptional evolutionary exploration exerted by coronavirus toward host recognition.

Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction

Infection of hamsters shows that one of the variants which carries deletion of 10 amino acids does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection, and it is suggested that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure.

The genetic structure of SARS‐CoV‐2 does not rule out a laboratory origin

  • R. SegretoYuri Deigin
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2020
The furin cleavage site in the spike protein of SARS‐CoV‐2 confers to the virus the ability to cross species and tissue barriers, but was previously unseen in other Sars‐like CoVs.

The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins

It is demonstrated that, in addition to human ACE2, the Spike glycoprotein of SARS-CoV-2 has a broad host tropism for mammalian ACE2 receptors, despite divergence in the amino acids at the Spike receptor binding site on these proteins.

Might SARS‐CoV‐2 Have Arisen via Serial Passage through an Animal Host or Cell Culture?

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.

Emergence of SARS-CoV-2 through Recombination and Strong Purifying Selection

Evidence of strong purifying selection around the receptor binding motif (RBM) in the spike gene and in other genes among bat, pangolin and human coronaviruses, indicating similar strong evolutionary constraints in different host species is shown.

SARS-CoV-2 is well adapted for humans. What does this mean for re-emergence?

It is suggested that by the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS -CoV, and advocated for measured and effective approaches implemented in the 2002-2004 SARS outbreaks to identify lingering population of progenitor virus.

Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates

A protein structural analysis was employed to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 binding, and found the number of predicted unfavorable changes significantly correlated with the binding score.