Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (2)


SARS-CoV-2 Proteins
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    SARS-CoV-2 spike PROTEIN protein predicted to form stable complexes with host receptor protein orthologues from mammals, but not fish, birds or reptiles

    Authors: Su Datt Lam; Nicola Bordin; Vaishali P Waman; Harry M Scholes; Paul Ashford; Neeladri Sen; Lucy van Dorp; Clemens Rauer; Natalie L Dawson; Camilla SM Pang; Mahnaz Abbasian; Ian Sillitoe; Sarah JL Edwards; Jonathan G Lees; Joanne M Santini; Christine A Orengo

    doi:10.1101/2020.05.01.072371 Date: 2020-05-01 Source: bioRxiv

    SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S PROTEIN S-protein HGNC) binds to its receptor, ACE2 HGNC, and is then processed by TMPRSS2 HGNC. Whilst receptor binding contributes to the viral host range, S-protein PROTEIN S-protein HGNC: ACE2 HGNC complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein HGNC S-protein PROTEIN: ACE2 HGNC complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2 HGNC, and correlated these changes with COVID-19 MESHD infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 HGNC than TMPRSS2 HGNC. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.

    ACE2 HGNC Homo-dimerization, Human Genomic variants and Interaction of Host Proteins Explain High Population Specific Differences in Outcomes of COVID19 MESHD

    Authors: Swarkar Sharma; Inderpal Singh; Shazia Haider; Md. Zubbair Malik; Kalaiarasan Ponnusamy; Ekta Rai

    doi:10.1101/2020.04.24.050534 Date: 2020-04-24 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is a positive single-stranded RNA virus that causes a highly contagious Corona Virus Disease MESHD ( COVID19 MESHD). Entry of SARS-CoV-2 in human cells depends on binding of the viral spike (S) proteins PROTEIN to cellular receptor Angiotensin-converting enzyme 2 ( ACE2 HGNC) and on S-protein PROTEIN S-protein HGNC priming by host cell serine protease TMPRSS2 HGNC. Recently, COVID19 MESHD has been declared pandemic by World Health Organization (WHO) yet high differences in disease outcomes across countries have been seen. We provide evidences to explain these population-level differences. One of the key factors of entry of the virus in host cells presumably is because of differential interaction of viral proteins with host cell proteins due to different genetic backgrounds. Based on our findings, we conclude that a higher expression of ACE2 HGNC is facilitated by natural variations, acting as Expression quantitative trait loci (eQTLs), with different frequencies in different populations. We suggest that high expression of ACE2 HGNC results in homo-dimerization, proving disadvantageous for TMPRSS2 HGNC mediated cleavage of ACE2 HGNC; whereas, the monomeric ACE2 HGNC has higher preferential binding with SARS-CoV-2 S-Protein vis MESHD S-Protein PROTEIN S-Protein HGNC vis-a-vis its dimerized counterpart. Further, eQTLs in TMPRSS2 HGNC and natural structural variations in the gene may also result in differential outcomes towards priming of viral S-protein HGNC S-protein PROTEIN, a critical step for entry of the Virus in host cells. In addition, we suggest that several key host genes, like SLC6A19 HGNC, ADAM17 HGNC, RPS6 HGNC, HNRNPA1 HGNC, SUMO1 HGNC, NACA HGNC, BTF3 HGNC and some other proteases as Cathepsins, might have a critical role. To conclude, understanding population specific differences in these genes may help in developing appropriate management strategies for COVID19 MESHD with better therapeutic interventions.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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