Identifying Primate ACE2 Variants That Confer Resistance to SARS-CoV-2

SARS-CoV-2 infects humans through the binding of viral S-protein (spike protein) to human angiotensin I converting enzyme 2 (ACE2). The structure of the ACE2-S-protein complex has been deciphered and we focused on the 27 ACE2 residues that bind to S-protein. From human sequence databases, we identified nine ACE2 variants at ACE2–S-protein binding sites. We used both experimental assays and protein structure analysis to evaluate the effect of each variant on the binding affinity of ACE2 to S-protein. We found one variant causing complete binding disruption, two and three variants, respectively, strongly and mildly reducing the binding affinity, and two variants strongly enhancing the binding affinity. We then collected the ACE2 gene sequences from 57 nonhuman primates. Among the 6 apes and 20 Old World monkeys (OWMs) studied, we found no new variants. In contrast, all 11 New World monkeys (NWMs) studied share four variants each causing a strong reduction in binding affinity, the Philippine tarsier also possesses three such variants, and 18 of the 19 prosimian species studied share one variant causing a strong reduction in binding affinity. Moreover, one OWM and three prosimian variants increased binding affinity by >50%. Based on these findings, we proposed that the common ancestor of primates was strongly resistant to and that of NWMs was completely resistant to SARS-CoV-2 and so is the Philippine tarsier, whereas apes and OWMs, like most humans, are susceptible. This study increases our understanding of the differences in susceptibility to SARS-CoV-2 infection among primates.

Neoplasia in Prosimians: Case Series from a Captive Prosimian Population and Literature Review

Neoplastic diseases in prosimians have been sporadically reported in the literature. To provide a comprehensive review of prosimian neoplasia, a retrospective evaluation of neoplasia in a large captive prosimian colony and an extensive literature review were performed. Primates that belong to the Order Primata, Suborder Prosimii with histologic evidence of neoplasia were included. One hundred twenty-three cases of spontaneous neoplasia were identified in 101 prosimians from the Duke Lemur Center, and 124 cases were reported in 116 prosimians in the literature. Overall, this review compiled a total of 247 neoplasms in 217 prosimians. Of the 217 affected animals, 88 of 217 were males (41%), 100 of 217 were females (46%), and sex was not reported in 29 of 217 (13%). Ages ranged from 2 days to 36 years. Prosimian families represented were Lemuridae (80/217 [37%]), Cheirogaleidae (61/217 [28%]), Galagidae (44/217 [20%]), Lorisidae (28/217 [13%]), and Indriidae (4/217 [2%]). The most commonly affected species were the gray mouse lemur (Microcebus murinus) (28/217 [13%]), thick-tailed greater bush baby (Otolemur crassicaudatus) (23/217 [11%]), and black lemur (Eulemur macaco) (19/217 [9%]). Organ systems affected, in order of descending occurrence, were digestive (75/247 [30%]), reproductive (40/247 [16%]), hematopoietic (34/247 [14%]), integumentary (28/247 [11%]), endocrine (26/247 [11%]), and urinary (17/247 [7%]). The respiratory, nervous, musculoskeletal, and cardiovascular systems were infrequently affected. The most common neoplasms were hepatocellular (32/247 [13%]), lymphoma and/or leukemia (29/247 [12%]), biliary (15/247 [6%]), and mammary neoplasms (12/247 [5%]). This article should serve as a valuable reference for the types and relative frequencies of neoplasms that occur in prosimian species.