An acute respiratory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that surfaced in China in late 2019, continues to spread rapidly across the globe causing serious concerns. The coronavirus disease 2019 (COVID-19) is declared as a public health emergency worldwide by the World Health Organization (WHO). Increasing evidences have demonstrated human-to-human transmission that primarily affects the upper respiratory tract followed by lower respiratory tract damage leading to severe pneumonia. Based on the current status, the elderly population and people with prior co-morbidities are highly susceptible to serious health effects including cytokine up-regulation and acute respiratory distress syndrome (ARDS). Currently, COVID-19 research is still in the preliminary stage necessitating rigorous studies. There is no specific drug or vaccine targeting SARS-CoV-2 currently and only symptomatic treatment is being administered, but several antivirals are under active investigation. In this review, we have summarized the epidemiology, entry mechanism, immune response, and therapeutic implications, possible drug targets, their ongoing clinical trials, and put forward vital questions to offer new directions to the COVID-19 research.

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) infection, which has emerged as a global pandemic causing serious concerns. Lack of specific and effective therapeutics for the treatment of COVID-19 is a major concern and the development of vaccines is another important aspect in managing the infection effectively. The first step in the SARS-CoV-2 pathogenesis is the viral entry and it is mediated by its densely glycosylated spike protein (S-protein). Similar to the SARS-CoV, SARS-CoV-2 also engages angiotensin-converting enzyme 2 (ACE2) as the host cell entry receptor. In addition to ACE2, several recent studies have implicated the crucial role of cell surface heparan sulfate (HS) as a necessary assisting cofactor for ACE2mediated SARS-CoV-2 entry. Furthermore, SARS-CoV-2 was also identified to use both endosomal cysteine proteases cathepsin B and L (CatB/L) and the transmembrane serine protease 2 (TMPRSS2) for the pivotal role of S-protein priming mediating viral entry. As the entry of SARS-CoV-2 into host cells is mandatory for viral infection, it becomes an extremely attractive therapeutic intervention point. In this regard, this review will focus on the therapeutic targeting of the crucial steps of SARS-CoV-2 viral entry like S-protein/ACE2 interaction and S-protein priming by host cell proteases. In addition, this review will also give insights to the readers on several therapeutic opportunities, pharmacological targeting of the viral-entry facilitators like S-Protein, ACE2, cell surface HS, TMPRSS2, and CatB/L and evidence for those drugs currently ongoing clinical studies.

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Targeting one fibrotic signaling pathway at a time may not have any significant effect on the control of IPF. It is therefore recommended that future IPF management focuses on targeting multiple pro-fibrotic pathways associated with its complex pathogenesis.