Structural Basis of SARS-CoV-2 Spike Protein Priming by TMPRSS2

Mushtaq Hussain; Nusrat Jabeen; Anusha Amanullah; Ayesha Ashraf Baig; Basma Aziz; Sanya Shabbir; Fozia Raza

The recent pandemic of COVID-19 is the third outbreak of the diseases caused by beta coronavirus in humans, following Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS) (Cui et al., 2019) . By 13th March 2020, over 1.7 million of global population has been infected with mortality rate of 21% in closed cases (WHO COVID-19 situation report-84). Genetically, etiological agent of COVID-19, SARS-CoV-2, is closely related to SARS-CoV compared to MERS-CoV (Wu et al., 2020) . Similarly, like for SARS-CoV, Angiotensin Converting Enzyme-2 (ACE2) has been identified as the primary receptor for SARS-CoV-2 spike protein (Li, 2015; Lan et al., 2020) . Whereas MERS-CoV spike protein interacts with the DiPeptidyl Peptidase 4 (DPP4) as the first site of attachment to the host cell (Li, 2015) . Spike protein of SARS-CoV-2 is 1273 amino acid long protein with two functionally distinct regions, S1 and S2, involved in the attachment and entry of the virus, respectively. SARS-CoV-2 entry in the host cell is mediated by proteolytic cleavage of its spike protein, a process dubbed as priming. Recently, human Transmembrane Protease Serine 2 (TMPRSS2) has been shown to carry out the priming of the SARS-CoV-2 spike protein by generating two distinct fragments of the viral spike protein, S1/S2 and S2' (Hoffman et al.,