Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

SARS-CoV-2 S Protein Binding hACE2: Viral Entry, Pathogenesis, Prognosis, and Potential Therapeutic Targets

Version 1 : Received: 16 September 2020 / Approved: 18 September 2020 / Online: 18 September 2020 (04:56:02 CEST)

How to cite: Al-Zaidan, L.; Mestiri, S.; Raza, A.; Merhi, M.; Inchakalody, V.; Fernandez, Q.; Taib, N.; Uddin, S.; Dermime, S. SARS-CoV-2 S Protein Binding hACE2: Viral Entry, Pathogenesis, Prognosis, and Potential Therapeutic Targets. Preprints 2020, 2020090420 (doi: 10.20944/preprints202009.0420.v1). Al-Zaidan, L.; Mestiri, S.; Raza, A.; Merhi, M.; Inchakalody, V.; Fernandez, Q.; Taib, N.; Uddin, S.; Dermime, S. SARS-CoV-2 S Protein Binding hACE2: Viral Entry, Pathogenesis, Prognosis, and Potential Therapeutic Targets. Preprints 2020, 2020090420 (doi: 10.20944/preprints202009.0420.v1).

Abstract

Pneumonia cases of unknown etiology in Wuhan, China, were reported to the WHO on 31st of December 2019. Later the pathogen was reported to be a novel coronavirus designated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 is a novel pathogenic beta coronavirus that infects humans causing severe respiratory illness. However, multifarious factors can contribute to the susceptibility to COVID-19 related morbidity and mortality such as age, gender and underlying comorbidities. Importantly, SARS-CoV and SARS-CoV-2 entry into the host cells is mediated via ACE2 receptor. However, ACE2 receptor binding affinity to SARS-CoV-2 is 4 folds higher than that to SARS-CoV. Identification of different aspects such as binding affinity, differential antigenic profiles of spike glycoproteins, and ACE2 polymorphisms might influence the investigation of potential therapeutic strategies targeting SARS-CoV-2/ACE2 binding interface. Here we aim to elaborate on SARS-CoV-2 S1/ACE2 ligand that facilitates viral internalization as well as to highlight the differences between SARS-CoVs binding affinity to ACE2. We also discuss the possible immunogenic sequences of spike glycoprotein and the effect of ACE2 polymorphism on viral binding/infectivity and host susceptibility to disease. Furthermore, targeting of ACE2 will be discussed to understand its role in therapeutics.

Subject Areas

COVID-19; SARS-CoV-2; ACE2 receptor; spike glycoprotein; S glycoprotein immunogenic sequences; ACE2 polymorphism

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