SARS Cov 2: Science-only thread

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Re: SARS Cov 2: Science-only thread

Postby Joe Hillshoist » Mon May 18, 2020 9:00 pm

This is a 34 page paper suggesting the origin of SARS2 is a lab.

I dunno if it has been peer reviewed yet and I haven't fully gone thru cos it is proper hardcore science and tho I can follow it I'm no expert.

I'll post the abstract, intro and link and if people want and can follow it they can read the whole thing.

In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus

Sakshi Piplani1,2, Puneet Kumar Singh2, David A. Winkler3-6*, Nikolai Petrovsky1,2*
1 College of Medicine and Public Health, Flinders University, Bedford Park 5046, Australia
2 Vaxine Pty Ltd, 11 Walkley Avenue, Warradale 5046, Australia
3 La Trobe University, Kingsbury Drive, Bundoora 3042, Australia
4 Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Australia
5 School of Pharmacy, University of Nottingham, Nottingham NG7 2RD. UK
6 CSIRO Data61, Pullenvale 4069, Australia

*Joint senior authors


The devastating impact of the COVID-19 pandemic caused by SARS–coronavirus 2 (SARS- CoV-2) has raised important questions on the origins of this virus, the mechanisms of any zoonotic transfer from exotic animals to humans, whether companion animals or those used for commercial purposes can act as reservoirs for infection, and the reasons for the large variations in SARS-CoV-2 susceptibilities across animal species. Traditional lab-based methods will ultimately answer many of these questions but take considerable time. Increasingly powerful in silico modeling methods provide the opportunity to rapidly generate information on newly emerged pathogens to aid countermeasure development and also to predict potential future behaviors. We used an in silico structural homology modeling approach to characterize the SARS-CoV-2 spike protein which predicted its high affinity binding to the human ACE2 receptor. Next we sought to gain insights into the possible origins and transmission path by which SARS-CoV-2 might have crossed to humans by constructing models of the ACE2 receptors of relevant species, and then calculating the binding energy of SARS-CoV-2 spike protein to each of these. Notably, SARS-CoV-2 spike protein had the highest overall binding energy for human ACE2, greater than all the other tested species including bat, the postulated source of the virus. This indicates that SARS-CoV-2 is a highly adapted human pathogen. Of the species studied, the next highest binding affinity after human was pangolin, which is most likely explained by a process of convergent evolution. Binding of SARS-CoV-2 for dog and cat ACE2 was similar to affinity for bat ACE2, all being lower than for human ACE2, and is consistent with only occasional observations of infections of these domestic animals. Snake ACE2 had low affinity for spike protein, making it highly improbable that snakes acted as an intermediate vector. Overall, the data indicates that SARS-CoV-2 is uniquely adapted to infect humans, raising important questions as to whether it arose in nature by a rare chance event or whether its origins might lie elsewhere.

The devastating impact of COVID-19 infections caused by SARS–coronavirus 2 (SARS-CoV-2) has stimulated unprecedented international activity to discover effective vaccines and drugs for this and other pathogenic coronaviruses.1-16 It has also raised important questions on the mechanisms of zoonotic transfer of viruses from animals to humans, questions as to whether companion animals or those used for commercial purposes can act as reservoirs for infection, and the reasons for the large variations in SARS-CoV-2 susceptibility across animal species.17-19 Understanding how viruses move between species may help us prevent or minimize these pathways in the future. Elucidating the molecular basis for the different susceptibilities of species may also shed light on the differences in susceptibilities in different sub-groups of humans.

Very recently, Shi et al. published the results of experiments to determine the susceptibility to SARS-CoV-2 of ferrets, cats, dogs, and other domesticated animals.20 They showed that SARS- CoV-2 virus replicates poorly in dogs, pigs, chickens, and ducks, but ferrets and cats are permissive to infection. Other studies have reported the susceptibility of other animal species to SARS-CoV-2.17,20,21 Susceptible species such as macaques, hamsters and ferrets are used as animal models of SARS-CoV-2 infection.22-24 In the absence of purified, isolated ACE2 from all the relevant animal species that could be used to measure the molecular affinities to spike protein experimentally, computational methods offer considerable promise for determining the rank order of affinities across species, as a method to impute which species may be permissive to SARS-CoV-2.

Here we show how computational chemistry methods from structure-based drug design can be used to determine the relative binding affinities of the SARS-CoV-2 spike protein for its receptor, angiotensin converting enzyme (ACE)-2, a critical initiating event for SARS-CoV-2 infection, across multiple common and exotic animal species.25-27 The aim of these studies was to better understand the species-specific nature of this interaction and see if this could help elucidate the origin of SARS-CoV-2 and the mechanisms for its zoonotic transmission.
Joe Hillshoist
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