Comparative ACE2 variation and primate COVID-19 risk
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Abstract
The emergence of SARS-CoV-2 has caused over a million human deaths and massive global disruption. The viral infection may also represent a threat to our closest living relatives, nonhuman primates. The contact surface of the host cell receptor, ACE2, displays amino acid residues that are critical for virus recognition, and variations at these critical residues modulate infection susceptibility. Infection studies have shown that some primate species develop COVID-19-like symptoms; however, the susceptibility of most primates is unknown. Here, we show that all apes and African and Asian monkeys (catarrhines), exhibit the same set of twelve key amino acid residues as human ACE2. Monkeys in the Americas, and some tarsiers, lemurs and lorisoids, differ at critical contact residues, and protein modeling predicts that these differences should greatly reduce SARS-CoV-2 binding affinity. Other lemurs are predicted to be closer to catarrhines in their susceptibility. Our study suggests that apes and African and Asian monkeys, and some lemurs, are likely to be highly susceptible to SARS-CoV-2. Urgent actions have been undertaken to limit the exposure of great apes to humans, and similar efforts may be necessary for many other primate species.
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SciScore for 10.1101/2020.04.09.034967: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Coding sequences were translated using Geneious Version 9.1.8 and we aligned both nucleotide and amino acid sequences with MAFFT41. Geneioussuggested: (Geneious, RRID:SCR_010519)To visualize patterns of gene conservation across taxa and identify the congruence of the ACE2 gene tree with currently accepted phylogenetic relationships among species, we reconstructed trees using both Bayesian (MrBayes 3.2.642) and Maximum Likelihood (RAxML 8.2.1143) methods with 200,000 MCMC cycles and 1,000 bootstrap replicates, respectively (code available on GitHub44). MrBayessuggested: (MrBayes, RRID:SCR_012…SciScore for 10.1101/2020.04.09.034967: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Coding sequences were translated using Geneious Version 9.1.8 and we aligned both nucleotide and amino acid sequences with MAFFT41. Geneioussuggested: (Geneious, RRID:SCR_010519)To visualize patterns of gene conservation across taxa and identify the congruence of the ACE2 gene tree with currently accepted phylogenetic relationships among species, we reconstructed trees using both Bayesian (MrBayes 3.2.642) and Maximum Likelihood (RAxML 8.2.1143) methods with 200,000 MCMC cycles and 1,000 bootstrap replicates, respectively (code available on GitHub44). MrBayessuggested: (MrBayes, RRID:SCR_012067)RAxMLsuggested: (RAxML, RRID:SCR_006086)We had to exclude Hipposideros pratti and Myotis daubentonii from PAML analyses, because only a partial ACE2 sequence was available for these two species. PAMLsuggested: (PAML, RRID:SCR_014932)Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:There are a number of important caveats to our study. Firstly, all of our predictions are based on interpretations of gene and resultant amino acid sequences, rather than based on direct assessment of individual responses to induced infection. Nonetheless, the overall pattern of our results is being borne out by infection studies on a few species that are used as biomedical models. So far, all catarrhine species tested by infection studies, including rhesus macaques, longtailed macaques, and vervet monkeys13,14,64 have exhibited COVID-19-like symptoms in response to infection, including large lung and other organ lesions13 and cytokine storms14. In contrast, marmosets did not exhibit major symptoms in response to infection13. While these results support and validate our findings based on ACE2 sequence interpretation, the number of primate species that can and will be tested directly by infection studies will be restricted to just a handful. Our study enhances this picture, by allowing inferences to be made across the primate radiation, backed up by the published infection studies on a few target model species. Some of our results, such as the uniform conservation of ACE2 among catarrhines, backed up by the demonstrated high susceptibility of humans and other catarrhines to SARS-CoV-2, should give a good degree of confidence of high levels of risk. Given the identical residues of humans to other apes and monkeys in Asia and Africa at the target site, it seems unlikely that the...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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- No protocol registration statement was detected.
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