Variation in predicted COVID-19 risk among lemurs and lorises

Abstract

The novel coronavirus SARS-CoV-2, which in humans leads to the disease COVID-19, has caused global disruption and more than 2 million fatalities since it first emerged in late 2019. As we write, infection rates are at their highest point globally and are rising extremely rapidly in some areas due to more infectious variants. The primary target of SARS-CoV-2 is the cellular receptor angiotensin-converting enzyme-2 (ACE2). Recent sequence analyses of the ACE2 gene predict that many nonhuman primates are also likely to be highly susceptible to infection. However, the anticipated risk is not equal across the Order. Furthermore, some taxonomic groups show high ACE2 amino acid conservation, while others exhibit high variability at this locus. As an example of the latter, analyses of strepsirrhine primate ACE2 sequences to date indicate large variation among lemurs and lorises compared to other primate clades despite low sampling effort. Here, we report ACE2 gene and protein sequences for 71 individual strepsirrhines, spanning 51 species and 19 genera. Our study reinforces previous results while finding additional variability in other strepsirrhine species, and suggests several clades of lemurs have high potential susceptibility to SARS-CoV-2 infection. Troublingly, some species, including the rare and endangered aye-aye (Daubentonia madagascariensis), as well as those in the genera Avahi and Propithecus, may be at high risk. Given that lemurs are endemic to Madagascar and among the primates at highest risk of extinction globally, further understanding of the potential threat of COVID-19 to their health should be a conservation priority. All feasible actions should be taken to limit their exposure to SARS-CoV-2.

Figure 1

Amino acid composition of the ACE2 protein at sites that are critical for interacting with the SARS‐CoV‐2 receptor binding domain across examined strepsirrhine genera, with respect to the human ACE2 sequence. The phylogenetic relationship among studied species is presented centrally, with branch lengths representing approximate evolutionary distances. (ACE2 = angiotensin‐converting enzyme‐2)

Figure 2

Model of human ACE2 in complex with SARS‐CoV‐2 RBD is presented in Panel (a). Three of the key ACE2 interfacial residues are highlighted in Panel (b). The dashed lines indicate predicted hydrogen bonding interactions. Interactions at three of the critical binding sites (41, 42, and 82) are shown for humans and other catarrhines (i.e., apes and monkeys in Africa and Asia). Changes in amino acids diminish these binding interactions. For example, substitution of tyrosine with histidine at site 41 in Panel (c) decreases the viral‐RBD binding affinity by removal of the potential hydrogen‐bonding interactions with T500 and N501. (ACE2 = angiotensin‐converting enzyme‐2; RBD = receptor‐binding domain)