The molecular basis for SARS-CoV-2 recognized by dog ACE2

Abstract

SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin converting enzyme 2 (dACE2) can bind to SARS-CoV-2 spike (S) protein receptor binding region (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. we solved the crystal structure of RBD in complex with dACE2 and found that the total numbers of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that to hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2, and need intense monitoring and controlling.

Human-to-dog Transmission of SARS-CoV-2 Lota Variant: Should COVID-19 Patients Avoid Close Contact with their Pets During Illness?

“…In the other hand, in vitro studies have reported that N501Y mutation found in several variants such as Alpha (B.1.1.7), Gamma (P.1) and Delta (B.1.617.2) enhances the a nity of RBD towards dACE2, accounting for a 3-fold increase in a nity (K D =37.1). Hence, wild-type RBD (K D =123nM), augmented a nity and higher viral loads found in lineages carrying D614G mutation that was found in the present study, and it could cause an increase in human-to-animal transmission 22,24 .…”

“…Furthermore, it is important to emphasize that mutation D164G confers increased transmissibility to SARS-CoV-2 by stabilizing Spike protein, this prevents the S1 and S2 segments to be cleaved before RBD interacts with ACE2 receptor 23 . This could be associated with the greater a nity observed by Zhang et al 24 towards dog ACE2 (dACE2) of variants carrying D614G mutation when compared to Wu-1 SARS-CoV-2. Therefore, mutation D614G could play a key role for anthropozoonotic transmission of SARS-CoV-2 24 .…”

“…This could be associated with the greater a nity observed by Zhang et al 24 towards dog ACE2 (dACE2) of variants carrying D614G mutation when compared to Wu-1 SARS-CoV-2. Therefore, mutation D614G could play a key role for anthropozoonotic transmission of SARS-CoV-2 24 .…”

“…Predicted 3D models of spike protein domains, namely Amino-terminal Domain (NTD), Receptor Binding Domain (RBD), and S1/S2 were constructed in AlphaFold2 41 from the sequence of SARS-CoV-2 Iota (B.1.526) retrieved from the infected human, multiple sequence alignment for AlphaFold2 was done in MMseqs2 42 . Then, molecular docking analysis was carried out in HDOCK for comparing the a nity of wild-type SARS-CoV-2 RBD (wtRBD) (Protein Database accession ID 6M0J:B) 43 and Iota RBD towards both Human (hACE2) and dog (dACE2) 24 angiotensin converting enzyme 2 (6M0J:A and 7E3J:A respectively). Generated models for each interaction were ranked according to Standard binding free energy (ΔG°) 44 .…”

Neutralization of recombinant RBD-subunit vaccine ZF2001-elicited antisera to SARS-CoV-2 variants including Delta

“…Another three important variants of interest (VOIs), Epsilon (B.1.429 lineage), Eta (B.1.525 lineage) and Kappa (B.1.617.1 lineages), were also included. SARS-CoV-2 Wild type strain (Wuhan-1 reference strain) was tested for comparison 16,17 . The mutation site of each variant in spike was listed in Supplementary Fig.…”