Journal Article

ACE2 and TMPRSS2 variation in savanna monkeys (Chlorocebus spp.): Potential risk for zoonotic/anthroponotic transmission of SARS-CoV-2 and a potential model for functional studies

Jasinska, Anna J., Bergey, Christina M., Burt, Felicity, Turner, Trudy R., Jorgensen, Matthew J., Freimer, Nelson B., Svardal, Hannes, Schmitt, Christopher A., Ramensky, Vasily, Grobler, J. Paul

2020

Overview

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has devastated health infrastructure around the world. Both ACE2 (an entry receptor) and TMPRSS2 (used by the virus for spike protein priming) are key proteins to SARS-CoV-2 cell entry, enabling progression to COVID-19 in humans. Comparative genomic research into critical ACE2 binding sites, associated with the spike receptor binding domain, has suggested that African and Asian primates may also be susceptible to disease from SARS-CoV-2 infection. Savanna monkeys (Chlorocebus spp.) are a widespread non-human primate with well-established potential as a bi-directional zoonotic/anthroponotic agent due to high levels of human interaction throughout their range in sub-Saharan Africa and the Caribbean. To characterize potential functional variation in savanna monkey ACE2 and TMPRSS2, we inspected recently published genomic data from 245 savanna monkeys, including 163 wild monkeys from Africa and the Caribbean and 82 captive monkeys from the Vervet Research Colony (VRC). We found several missense variants. One missense variant in ACE2 (X:14,077,550; Asp30Gly), common in Ch. sabaeus, causes a change in amino acid residue that has been inferred to reduce binding efficiency of SARS-CoV-2, suggesting potentially reduced susceptibility. The remaining populations appear as susceptible as humans, based on these criteria for receptor usage. All missense variants observed in wild Ch. sabaeus populations are also present in the VRC, along with two splice acceptor variants (at X:14,065,076) not observed in the wild sample that are potentially disruptive to ACE2 function. The presence of these variants in the VRC suggests a promising model for SARS-CoV-2 infection and vaccine and therapy development. In keeping with a One Health approach, characterizing actual susceptibility and potential for bi-directional zoonotic/anthroponotic transfer in savanna monkey populations may be an important consideration for controlling COVID-19 epidemics in communities with frequent human/non-human primate interactions that, in many cases, may have limited health infrastructure.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: ACE2 / Amino acids / Angiotensin-Converting Enzyme 2 / Animals / Betacoronavirus - metabolism / Binding sites / Biology and Life Sciences / Causes of / Cell receptors / Chlorocebus / Chlorocebus aethiops / Coronavirus Infections - genetics / Coronavirus Infections - transmission / Coronavirus Infections - veterinary / Coronaviruses / COVID-19 / Development and progression / Disease control / Disease Susceptibility / Disease transmission / Distribution / Ecology and Environmental Sciences / Epidemics / Funding / Health aspects / Infections / Infrastructure / Medical research / Medicine and Health Sciences / Monkeys / Mutation / Neurosciences / Pandemics / Pandemics - veterinary / People and places / Peptidyl-Dipeptidase A - genetics / Physiological aspects / Pneumonia, Viral - genetics / Pneumonia, Viral - transmission / Pneumonia, Viral - veterinary / Populations / Preventive medicine / Primate Diseases - genetics / Primates / Priming / Proteases / Proteins / Receptors / Respiratory diseases / SARS-CoV-2 / Savannahs / Serine Endopeptidases - genetics / Severe acute respiratory syndrome / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus - metabolism / Spike protein / Urban areas / Vaccines / Vervet monkey / Viral diseases / Virology / Viruses / Whole Genome Sequencing / Zoonoses / Zoonoses - transmission