Drug targets for corona virus: A systematic review

Prajapat, Manisha; Sarma, Phulen; Shekhar, Nishant; Avti, Pramod K.; Sinha, Sanjib; Kaur, Hardeep; Kumar, Subodh; Bhattacharyya, Anusuya; Kumar, Harish; Bansal, Seema; Medhi, Bikash

doi:10.4103/ijp.ijp_115_20

Cited by 392 publications

(186 citation statements)

References 83 publications

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“…Current drugs have limited efficacy in treating CoV in different populations and species. Given the high incidence of CoV resistance, especially in immunocompromised patients, the design of new drugs that target specific activities of the virus and stop one or more stages of its infection cycle is essential (Prajapat et al, 2020;Yang et al, 2020;Zhou & Zhao, 2020). In recent years, most research has focused on blocking virus transmission to the HC, RNA polymerase activity of the virus, and HC-virus interactions (Schaack & Mehle, 2019).…”

Section: Enzyme Inhibitors As Therapeutic Platformsmentioning

confidence: 99%

A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin

Hasan

Paray

Hussain³

et al. 2020

Journal of Biomolecular Structure and Dynamics

269

239

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The widespread antigenic changes lead to the emergence of a new type of coronavirus (CoV) called as severe acute respiratory syndrome (SARS)-CoV-2 that is immunologically different from the previous circulating species. Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furincleavage site results in the SARS-CoV-2 invasion. Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. As several kinds of CoVs, from various genera, have at their S1/S2 binding site a preserved site, we further surveyed the role of furin cleavage site (FCS) on the life cycle of the CoV. Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic. Finally, some ongoing challenges and future prospects for the development of potential drugs to promote targeting specific activities of the CoV were reviewed. In conclusion, this review may pave the way for providing useful information about different compounds involved in improving the effectiveness of CoV vaccine or drugs with minimum toxicity against human health. ARTICLE HISTORY

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Section: Enzyme Inhibitors As Therapeutic Platformsmentioning

confidence: 99%

A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin

Hasan

Paray

Hussain³

et al. 2020

Journal of Biomolecular Structure and Dynamics

269

239

View full text Add to dashboard Cite

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“…Using the developed assay, we ran a pilot screen to assess the activity of 148 small molecules with suspected therapeutic potential against coronavirus infections mined from the available literature 11 (RZ' = 0.84). We identified 19 compounds with an EC 50 < 9.6 µM and, based on data obtained from an uninfected HeLa-ACE2 24-hour live/dead assay, 10 of these were selective (uninfected HeLa-ACE2 CC 50 /SARS-CoV-2 EC 50 > 10 or uninfected HeLa-ACE2 CC 50 > 40 µM) (Table S1).…”

Section: High-throughput Cell-based Phenotypic Assay Against Sars-cov-2mentioning

confidence: 99%

Oral drug repositioning candidates and synergistic remdesivir combinations for the prophylaxis and treatment of COVID-19

Bakowski

Beutler

Chen

et al. 2020

Preprint

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The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. A high-throughput, high-content imaging assay of human HeLa cells expressing the SARS-CoV-2 receptor ACE2 was used to screen ReFRAME, a best-in-class drug repurposing library. From nearly 12,000 compounds, we identified 66 compounds capable of selectively inhibiting SARS-CoV-2 replication in human cells. Twenty-four of these drugs show additive activity in combination with the RNA-dependent RNA polymerase inhibitor remdesivir and may afford increased in vivo efficacy. We also identified synergistic interaction of the nucleoside analog riboprine and a folate antagonist 10deazaaminopterin with remdesivir. Overall, seven clinically approved drugs (halofantrine, amiodarone, nelfinavir, simeprevir, manidipine, ozanimod, osimertinib) and 19 compounds in other stages of development may have the potential to be repurposed as SARS-CoV-2 oral therapeutics based on their potency, pharmacokinetic and human safety profiles.

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“…The COVID-19 pandemic has created an urgent need for effective and rapidly deployable therapeutics [1,2].…”

Section: Introductionmentioning

confidence: 99%

Computational Target-Based Drug Repurposing of Elbasvir, an Antiviral Drug Predicted to Bind Multiple SARS-CoV-2 Proteins

Balasubramaniam

2020

Preprint

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Coronavirus disease 19 (COVID-19) is a severe acute respiratory syndrome caused by SARS-CoV-2 (2019-nCoV). While no drugs have yet been approved to treat this disease, small molecules effective against other viral infections are under clinical evaluation for therapeutic abatement of SARS-CoV-2 infections. Ongoing clinical trials include Kaletra (a combination of two protease inhibitors approved for HIV treatment), remdesivir (an investigational drug targeting RNA-dependent RNA polymerase [RdRP] of SARS-CoV-2), and hydroxychloroquine (an approved anti-malarial and immuno-modulatory drug). Since SARS-CoV-2 replication depends on three virally encoded proteins (RdRP, papain-like proteinase, and helicase), we screened 54 FDAapproved antiviral drugs and ~3300 investigational drugs for binding to these proteins using targeted and unbiased docking simulations and computational modeling. Elbasvir, a drug approved for treating hepatitis C, is predicted to bind stably and preferentially to all three proteins. At the therapeutic dosage, elbasvir has low toxicity (liver enzymes transiently elevated in 1% of subjects) and well-characterized drug-drug interactions.We predict that treatment with elbasvir, alone or in combination with other drugs such as grazoprevir, could efficiently block SARS-CoV-2 replication. The concerted action of elbasvir on at least three targets essential for viral replication renders viral mutation to drug resistance extremely unlikely. Author SummaryWe performed in silico screens of FDA-approved and investigational drugs, to seek rapidly deployable agents that could be combined to disrupt multiple viral targets. One drug stood out with exceptionally stable binding to the three initial protein targets essential for SARS-CoV-2 replication: elbasvir, currently approved as one component of Zepatier TM (Merck) for treatment of chronic hepatitis C infections. Elbasvir was in the top decile of drugs for stable binding to each of 6 SARS-CoV-2 proteins, and thus is predicted to confer a multi-pronged defence against COVID-19, either alone or in combination with other anti-viral drugs.

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Drug targets for corona virus: A systematic review

Cited by 392 publications

References 83 publications

A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin

A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin

Oral drug repositioning candidates and synergistic remdesivir combinations for the prophylaxis and treatment of COVID-19

Computational Target-Based Drug Repurposing of Elbasvir, an Antiviral Drug Predicted to Bind Multiple SARS-CoV-2 Proteins

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