Predicting the Animal Susceptibility and Therapeutic Drugs to SARS-CoV-2 Based on Spike Glycoprotein Combined With ACE2

Abstract

Recently, a few animals have been frequently reported to have been diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether they are SARS-CoV-2 intermediate hosts is worthy of great attention. The interaction of SARS-CoV-2 spike protein and its acceptor protein ACE2 is an important issue in determining viral host range and cross-species infection, while the binding capacity of Spike protein to ACE2 of different species is unknown. Here, we used the atomic structure model of SARS-CoV-2 and human ACE2 to assess the receptor utilization capacity of ACE2s from 10 kinds of animals. Results show that chimpanzees, domestic cats and cattles are more susceptible to infection by SARS-CoV-2. Cats in particular, such as pet cats and stray cats, interact very closely with humans, implying the necessity to carefully evaluate the risk of cats during the current COVID-19 pandemic. Furthermore, based on ACE2(cats)-SARS-CoV-2-RBD model, through high-throughput screening methods using a pool of 30,000 small molecules, eight compounds were selected for binding free energy calculations. All the eight compounds can effectively interfere with the binding of ACE2 and Spike protein, especially Nelfinavir, providing drug candidates for the treatment and prevention of SARS-CoV-2, suggesting further assessment of the anti-SARS-CoV-2 activity of these compounds in cell culture. Although we only reported the results of the simulation, and more laboratory and epidemiological investigation are required. Like cats are a risk factor, we can further detect SARS-CoV-2 according to the susceptibility of different animals, find the potential host of infection, and completely cut off the living space of the virus. Especially, cats could be a choice of animal model for screening antiviral drugs or vaccine candidates against SARS-CoV-2.

The Upper Respiratory Tract of Felids Is Highly Susceptible to SARS-CoV-2 Infection

“…Among feline species, the amino acid sequence of ACE2 is highly conserved, and human and feline ACE2 share a homology of 85% in total and 80% referring to the residues involved in SARS-CoV-2 attachment ( Supplementary Material Figure S1a ). In consistence with previous studies [ 32 , 33 , 34 ], we showed that feline ACE2 is capable of mediating SARS-CoV-2 S-driven entry as efficiently as human ACE2. Investigations on the expression levels of ACE2 within the respiratory tract of felids revealed that the highest amounts of ACE2 mRNA and protein were detected in nasal mucosa, whereas only limited expression was observed in lung tissue.…”

Investigating the active compounds and mechanism of HuaShi XuanFei formula for prevention and treatment of COVID-19 based on network pharmacology and molecular docking analysis

“…Based on the structures of SARS-CoV-2, 3C-like (3CL) protease hydrolase has been identified as a potential target against COVID-19, because it can inhibit the replication of CoV [ 13 ]. Meanwhile, angiotensin-converting enzyme 2 (ACE2) has a great affinity with the spike protein of SARS-CoV-2[ 14 ]. Therefore, ACE2 and 3CL were considered as receptors in molecular docking.…”

Animal Transmission of SARS-CoV-2 and the Welfare of Animals during the COVID-19 Pandemic

“…A structural analysis identified 20 residues of the human ACE2 receptor that contact the SARS-CoV-2 spike protein receptor binding domain; members of the Felidae share 16 out of the 20 contacting residues [173]. Another structural analysis of the ACE2 receptor identified 13 binding domain contacting residues of the human ACE2 receptor; domestic cats share 12 of these 13, and they also share with humans 14 of the 15 hydrogen bonds at the SARS-CoV-2 RBD/ACE2 interface [174]. A third study reported 14 human ACE2-contacting residues with both domestic cats and tigers sharing 11 of the 14 [175].…”