Recent Advances in Pathophysiology, Drug Development and Future Perspectives of SARS-CoV-2

Singh, Desh Deepak; Han, Ihn; Choi, Eun-Ha; Yadav, Dharmendra Kumar

doi:10.3389/fcell.2020.580202

Cited by 23 publications

(22 citation statements)

References 141 publications

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“…Since it mainly affects lungs through the respiratory tract, hence named Severe Acute Respiratory Syndrome (SARS). SARS-CoV-1 has affected nearly 29 countries with the total confirmed cases 8096 and 774 deaths with the fatality rate (FR, the proportion of people died with certain disease among the total diagnosed individuals) of 9.6% [ 16 ]. This was followed by MERS (Middle East Respiratory Syndrome) outbreak in Saudi Arabia (June 2012), which was also caused by the same family of coronavirus named MERS-CoV (MERS coronavirus).…”

Section: Discovery/history Of Coronavirusmentioning

confidence: 99%

“…This was followed by MERS (Middle East Respiratory Syndrome) outbreak in Saudi Arabia (June 2012), which was also caused by the same family of coronavirus named MERS-CoV (MERS coronavirus). Since then, MERS-CoV has affected 26 countries with confirmed 2519 cases and 866 deaths with an FR of 34.4% [ 16 ]. Currently, COVID-19, still spreading, is caused by SARS-CoV-2.…”

Section: Discovery/history Of Coronavirusmentioning

confidence: 99%

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COVID-19 Vaccines (Revisited) and Oral-Mucosal Vector System as a Potential Vaccine Platform

et al. 2021

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There are several emerging strategies for the vaccination of COVID-19 (SARS-CoV-2) however, only a few have yet shown promising effects. Thus, choosing the right pathway and the best prophylactic options in preventing COVID-19 is still challenging at best. Approximately, more than two-hundred vaccines are being tested in different countries, and more than fifty clinical trials are currently undergoing. In this review, we have summarized the immune-based strategies for the development of COVID-19 vaccines and the different vaccine candidate platforms that are in clinical stages of evaluation, and up to the recently licensed mRNA-based COVID-19 vaccines of Pfizer-BioNtech and Moderna’s. Lastly, we have briefly included the potentials of using the ‘RPS-CTP vector system’ for the development of a safe and effective oral mucosal COVID-19 vaccine as another vaccine platform.

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Section: Discovery/history Of Coronavirusmentioning

confidence: 99%

Section: Discovery/history Of Coronavirusmentioning

confidence: 99%

COVID-19 Vaccines (Revisited) and Oral-Mucosal Vector System as a Potential Vaccine Platform

et al. 2021

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“…SARS-CoV-2 M pro mediates viral replication and transcription making it an appealing drug target [40]. SARS-CoV-2 M pro has one polypeptide and three domains with the CYS-HIS catalytic dyad and is highly conserved between M pro in all coronaviruses indicating that inhibition of this pocket could result in broad-spectrum activity against other coronaviruses [41].…”

Section: Structure and Function Of Sars-cov-2 M Promentioning

confidence: 99%

“…Ibuprofen was also shown to covalently bond to the cysteine residue of SARS-CoV-2 M pro . Furthermore, as mentioned in chapter 1, drugs that bind to the CYS-HIS (CYS-145 and HIS-41) catalytic dyad found in the SARS-CoV-2 M pro cleft are more likely to exhibit a broad-spectrum of inhibition with other SARS-CoV-2 proteases [41] like the 3-chymotrypsin-like protease (3CLpro) present on the 3' end which initiates coronavirus replication [63].…”

Section: Important Amino Acids To Consider For Future Drug Developments Against Covid-19mentioning

confidence: 99%

Molecular Docking Study of the Binding Interaction of Hydroxychloroquine, Dexamethasone and Other Anti-Inflammatory Drugs with SARS-CoV-2 Protease and SARS-CoV-2 Spikes Glycoprotein

Adebambo¹,

Haji²

2021

CMB

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Aims: The outbreak of the novel coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still accountable for millions of deaths worldwide and declared as a global pandemic by the World Health Organisation. Despite efforts, there is still limited evidence available on a successful potent inhibitor with a low toxicity profile that can aid in the prevention and/or treatment of COVID-19. This study will focus on four main aspects: 1) screening 19 Food Drug and Administration (FDA) approved drugs using computational molecular docking; 2) assessing drug toxicity profiles using biological data; 3) recommending potential therapies against COVID-19 and 4) supplementing currently used therapies. Methods: 19 FDA approved drugs were investigated against the crystal structure of SARS-CoV-2 protease (6LU7) and SARS-CoV-2 glycoprotein (6VXX) using a computational molecular docking software, Molecular Operating Environment (MOE). Separately, on MOE, 6LU7 and 6VXX were loaded, prepared, and the binding pockets located. The drug's canonical SMILES were imported, minimised, and docked on the prepared proteins using a search algorithm to establish the highest stability conformation. Drugs were ranked depending on binding properties and biological data to assess safety; steric clashes and voids in the binding site were also analysed. Results and discussion: Out of the nineteen (19) FDA approved drugs, 18 inhibited 6LU7 and 13 inhibited 6VXX. High-ranked drugs based on binding properties for 6LU7 were hydroxychloroquine, dexamethasone, naproxen, etoricoxib, and ibuprofen.

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“…Currently, disease control has been based on symptom management, including the use of convalescent plasma, synthetic antibodies, interferon, low-dose corticosteroids, IL-1 and IL-16 inhibitors, Azithromycin, Remdesivir, Baricitinib, Lopinavir/Ritonavir, Hydroxychloroquine, and, in severe cases, supportive care (oxygen and mechanical ventilation) [4, 5]. Although there may be approved drugs [6], there is still no conclusive information on their effectiveness and they have limited uses.…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin effectively inhibits late replicative cycle steps of SARS-CoV-2in vitro

Flórez-Álvarez

Zapata

et al. 2021

Preprint

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Introduction: SARS-CoV-2 has caused a pandemic of historic proportions and continues to spread worldwide. Currently, there is no effective therapy against this virus. This article evaluated the in vitro antiviral effect of Atorvastatin against SARS-CoV-2 and also identified the interaction affinity between Atorvastatin and three SARS-CoV-2 proteins, using in silico structure-based molecular docking approach. Materials and methods: The antiviral activity of Atorvastatin against SARS-CoV-2 was evaluated by three different treatment strategies using a clinical isolate of SARS-CoV-2. The interaction of Atorvastatin with Spike, RNA-dependent RNA polymerase (RdRp) and 3C-like protease (3CLpro) was evaluated by molecular docking. Results: Atorvastatin showed anti-SARS-CoV-2 activity of 79%, 54.8%, 22.6% and 25% at 31.2, 15.6, 7.9, and 3.9 µM, respectively, by pre-post-treatment strategy. In addition, atorvastatin demonstrated an antiviral effect of 26.9% at 31.2 µM by pre-infection treatment. This compound also inhibited SARS-CoV-2 in 66.9%, 75%, 27.9% and 29.2% at concentrations of 31.2, 15.6, 7.9, and 3.9 µM, respectively, by post-infection treatment. The interaction of atorvastatin with SARS-CoV-2 Spike, RdRp and 3CL protease yielded a binding affinity of -8.5 Kcal/mol, -6.2 Kcal/mol, and -7.5 Kcal/mol, respectively. Conclusion: Our study demonstrated the in vitro anti-SARS-CoV-2 activity of Atorvastatin, mainly against the late steps of the viral replicative cycle. A favorable binding affinity with viral proteins by bioinformatics methods was also shown. Due to its low cost, availability, well-established safety and tolerability, and the extensive clinical experience of atorvastatin, it could prove valuable in reducing morbidity and mortality from COVID-19.

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Recent Advances in Pathophysiology, Drug Development and Future Perspectives of SARS-CoV-2

Cited by 23 publications

References 141 publications

COVID-19 Vaccines (Revisited) and Oral-Mucosal Vector System as a Potential Vaccine Platform

COVID-19 Vaccines (Revisited) and Oral-Mucosal Vector System as a Potential Vaccine Platform

Molecular Docking Study of the Binding Interaction of Hydroxychloroquine, Dexamethasone and Other Anti-Inflammatory Drugs with SARS-CoV-2 Protease and SARS-CoV-2 Spikes Glycoprotein

Atorvastatin effectively inhibits late replicative cycle steps of SARS-CoV-2in vitro

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