Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors-The Current Status.

Autor:	Beeraka NM; Department of Biochemistry, Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), JSS Academy of Higher Education & Research (JSS AHER), Mysore, India., Sadhu SP; AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, India., Madhunapantula SV; Department of Biochemistry, Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), JSS Academy of Higher Education & Research (JSS AHER), Mysore, India.; Special Interest Group in Cancer Biology and Cancer Stem Cells (SIG-CBCSC), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysore, India., Rao Pragada R; AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, India., Svistunov AA; I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia., Nikolenko VN; I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.; Department of Normal and Topographic Anatomy, M.V. Lomonosov Moscow State University, Moscow, Russia., Mikhaleva LM; Research Institute of Human Morphology, Moscow, Russia., Aliev G; Research Institute of Human Morphology, Moscow, Russia.; Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.; Institute of Physiologically Active Compounds, Russian Academy of Sciences, Moscow, Russia.; GALLY International Research Institute, San Antonio, TX, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2020 Sep 18; Vol. 11, pp. 552925. Date of Electronic Publication: 2020 Sep 18 (Print Publication: 2020).
DOI:	10.3389/fimmu.2020.552925
Abstrakt:	Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease - 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. The clinical manifestations of this disease are pneumonia, lung injury, inflammation, and severe acute respiratory syndrome (SARS). Currently, there is no vaccine or effective pharmacological agents available for the prevention/treatment of SARS-CoV2 infections. Moreover, development of a suitable vaccine is a challenging task due to antibody-dependent enhancement (ADE) and Th-2 immunopathology, which aggravates infection with SARS-CoV-2. Furthermore, the emerging SARS-CoV-2 strain exhibits several distinct genomic and structural patterns compared to other coronavirus strains, making the development of a suitable vaccine even more difficult. Therefore, the identification of novel small molecule inhibitors (NSMIs) that can interfere with viral entry or viral propagation is of special interest and is vital in managing already infected cases. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, the development of novel inhibitors of ACE2/TMPRSS2 is likely to be beneficial in combating SARS-CoV-2 infections. However, the usage of ACE-2 inhibitors to block the SARS-CoV-2 viral entry requires additional studies as there are conflicting findings and severe health complications reported for these inhibitors in patients. Hence, the current interest is shifted toward the development of NSMIs, which includes natural antiviral phytochemicals and Nrf-2 activators to manage a SARS-CoV-2 infection. It is imperative to investigate the efficacy of existing antiviral phytochemicals and Nrf-2 activators to mitigate the SARS-CoV-2-mediated oxidative stress. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs. (Copyright © 2020 Beeraka, Sadhu, Madhunapantula, Rao Pragada, Svistunov, Nikolenko, Mikhaleva and Aliev.)
Databáze:	MEDLINE
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