Repurposing Artemisia annua L. Flavonoids, Artemisinin and Its Derivatives as Potential Drugs Against Novel Coronavirus (SARS –nCoV) as Revealed by In-Silico Studies

Coronavirus-induced COVID-19, a highly contagious respiratory illness first originated from Wuhan city of Hubei province, China, and has affected 235 countries across the globe. The COVID-19 is mainly transmitted by the droplets of an infected person when they cough, sneeze, or exhale. Currently, there are no specific drugs licensed for the effective treatment or prevention of COVID-19 and the treatment is mainly focused on controlling symptoms. Identification of small bioactive plant molecules that specifically target whole viral replication apparatus have great potential towards the development of antiviral drug discovery. This communication describes our current understanding of SARS-nCoV interaction with some herbal bioactive compounds of A. annua including sesquiterpenes, flavonoids and phenolics using in silico approach. Int. J. Appl. Sci. Biotechnol. Vol 8(4): 374-393

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Responding to the COVID-19 pandemic in Ghana

Ghana Medical Journal ◽

10.4314/gmj.v54i2.1 ◽

2020 ◽

Vol 54 (2) ◽

pp. 72-73

Author(s):

Ernest Kenu ◽

Joseph Frimpong ◽

Kwadwo Koram

Keyword(s):

Respiratory Distress ◽

Distress Syndrome ◽

Rna Virus ◽

Respiratory Illness ◽

The United States ◽

World Health ◽

Infected Person ◽

Wuhan City ◽

Novel Coronavirus ◽

Health Organization

On 12 January 2020, the World Health Organization (WHO) confirmed that a novel coronavirus was the cause of a respiratory illness in a cluster of people in Wuhan City, Hubei Province, China. The disease was christened COVID-19 and the pathogen (an RNA virus) identified as SARS-Coronavirus-2 (SARS-CoV-2).1,2 The virus is primarily spread through contact with small droplets produced from coughing, sneezing, or talking by an infected person. While a substantial proportion of infected individuals may remain asymptomatic, the most common symptoms in clinical cases include, fever, cough, acute respiratory distress, fatigue, and failure to resolve over 3 to 5 days of antibiotic treatment. Complications may include pneumonia and acute respiratory distress syndrome.3 Over five million confirmed cases of COVID-19 has been recorded globally with more than 300,000 deaths as at 25th May 2020. The United States of America has recorded the highest number of cases with more than 1.5 million and over 100,000 deaths.4 In Africa, more than 90,0000 cases have been reported with about 3,000 deaths. South Africa has recorded the highest number of cases with 23,615 cases and 481 deaths. Ghana confirmed its first cases of COVID-19 on 12th March 2020 and had as at 25 May 2020 recorded over 7,000 cases with 34 deaths.5

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An evidence-based systematic review on emerging therapeutic and preventive strategies to treat novel coronavirus (SARS-CoV-2) during an outbreak scenario

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0113 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Anupama M. Gudadappanavar ◽

Jyoti Benni

Keyword(s):

Antiviral Drug ◽

Drug Repurposing ◽

Respiratory Illness ◽

World Health ◽

Recombinant Vaccines ◽

Subunit Vaccines ◽

Coronavirus Infection ◽

Novel Coronavirus ◽

Health Organization ◽

Full Length Genome

AbstractA novel coronavirus infection coronavirus disease 2019 (COVID-19) emerged from Wuhan, Hubei Province of China, in December 2019 caused by SARS-CoV-2 is believed to be originated from bats in the local wet markets. Later, animal to human and human-to-human transmission of the virus began and resulting in widespread respiratory illness worldwide to around more than 180 countries. The World Health Organization declared this disease as a pandemic in March 2020. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. Nevertheless, few broad-spectrum antiviral drugs have been studied against COVID-19 in clinical trials with clinical recovery. In the current review, we summarize the morphology and pathogenesis of COVID-19 infection. A strong rational groundwork was made keeping the focus on current development of therapeutic agents and vaccines for SARS-CoV-2. Among the proposed therapeutic regimen, hydroxychloroquine, chloroquine, remdisevir, azithromycin, toclizumab and cromostat mesylate have shown promising results, and limited benefit was seen with lopinavir–ritonavir treatment in hospitalized adult patients with severe COVID-19. Early development of SARS-CoV-2 vaccine started based on the full-length genome analysis of severe acute respiratory syndrome coronavirus. Several subunit vaccines, peptides, nucleic acids, plant-derived, recombinant vaccines are under pipeline. This article concludes and highlights ongoing advances in drug repurposing, therapeutics and vaccines to counter COVID-19, which collectively could enable efforts to halt the pandemic virus infection.

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Screening of phytochemicals from Curcuma longa for their inhibitory activity on SARS-CoV-2: An in-silico study

Anti-Infective Agents ◽

10.2174/2211352519666210719090130 ◽

2021 ◽

Vol 19 ◽

Author(s):

Preeya Negi ◽

Lalita Das ◽

Surya Prakash ◽

Vaishali M. Patil

Keyword(s):

Drug Discovery ◽

In Silico ◽

Curcuma Longa ◽

Docking Studies ◽

Primary Objective ◽

In Silico Screening ◽

Rational Drug ◽

In Silico Study ◽

Speed Up ◽

Novel Coronavirus

Introduction: Natural products or phytochemicals have always been useful as effective therapeutics and for providing the lead for rational drug discovery approaches specific to anti-viral therapeutics. Methods: The ongoing pandemic caused by novel coronavirus has created a demand for effective therapeutics. Thus, to achieve the primary objective to search for effective anti-viral therapeutics, in silico screening of phytochemicals present in Curcuma longa extract (ex. Curcumin) has been planned. Results: The present work involves the evaluation of ADME properties and molecular docking studies. Conclusion: The application of rationalized drug discovery approaches to screen the diverse natural resources will speed up the anti-COVID drug discovery efforts and benefit the global community.

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Detailed Molecular Interactions of Favipiravir with SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza Virus Polymerases In Silico

Microorganisms ◽

10.3390/microorganisms8101610 ◽

2020 ◽

Vol 8 (10) ◽

pp. 1610 ◽

Cited By ~ 1

Author(s):

Mitsuru Sada ◽

Takeshi Saraya ◽

Haruyuki Ishii ◽

Kaori Okayama ◽

Yuriko Hayashi ◽

...

Keyword(s):

Influenza Virus ◽

Molecular Interactions ◽

In Silico ◽

Influenza A ◽

Active Sites ◽

Active Form ◽

Antiviral Drug ◽

Virus Rna ◽

Influenza A H1n1 ◽

In Silico Studies

Favipiravir was initially developed as an antiviral drug against influenza and is currently used in clinical trials against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19). This agent is presumably involved in RNA chain termination during influenza virus replication, although the molecular interactions underlying its potential impact on the coronaviruses including SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) remain unclear. We performed in silico studies to elucidate detailed molecular interactions between favipiravir and the SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza virus RNA-dependent RNA polymerases (RdRp). As a result, no interactions between favipiravir ribofuranosyl-5′-triphosphate (F-RTP), the active form of favipiravir, and the active sites of RdRps (PB1 proteins) from influenza A (H1N1)pdm09 virus were found, yet the agent bound to the tunnel of the replication genome of PB1 protein leading to the inhibition of replicated RNA passage. In contrast, F-RTP bound to the active sites of coronavirus RdRp in the presence of the agent and RdRp. Further, the agent bound to the replicated RNA terminus in the presence of agent, magnesium ions, nucleotide triphosphate, and RdRp proteins. These results suggest that favipiravir exhibits distinct mechanisms of action against influenza virus and various coronaviruses.

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Computational drug discovery of potential phosphodiesterase inhibitors using in silico studies

Asian Pacific Journal of Tropical Disease ◽

10.1016/s2222-1808(12)60272-2 ◽

2012 ◽

Vol 2 ◽

pp. S822-S826 ◽

Cited By ~ 1

Author(s):

Arumugam Madeswaran ◽

Muthuswamy Umamaheswari ◽

Kuppusamy Asokkumar ◽

Thirumalaisamy Sivashanmugam ◽

Varadharajan Subhadradevi ◽

...

Keyword(s):

Drug Discovery ◽

In Silico ◽

Phosphodiesterase Inhibitors ◽

In Silico Studies ◽

Computational Drug Discovery

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SARS-CoV-2 and COVID-19

10.33442/vt202144 ◽

2021 ◽

Author(s):

Rosalind Hollingsworth

Keyword(s):

Distress Syndrome ◽

Multiorgan Failure ◽

Mainland China ◽

Respiratory Illness ◽

Infected Person ◽

Increased Risk ◽

Asymptomatic Infections ◽

Novel Coronavirus ◽

Inflammatory Syndrome ◽

Respiratory Droplets

Coronavirus disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus which emerged in Wuhan, China in 2019, and from there spread to other parts of mainland China and around the world. The virus spreads mainly through respiratory droplets produced when an infected person coughs, sneezes, or speaks. On average, the time from exposure to SARS-CoV-2 to the appearance of symptoms is 5–6 days but can range from 1–14 days. Asymptomatic infections with SARS-CoV-2 can occur. In those with symptoms, most people (approx. 80%) will experience a mild to moderate respiratory illness and recover without hospital management. Adults 65 years of age and older, and individuals of any age with underlying medical conditions, are at increased risk for severe COVID-19 and death. Complications include respiratory failure, acute respiratory distress syndrome, sepsis/septic shock, thromboembolism, multiorgan failure and death. In rare cases, children and adults can develop a severe inflammatory syndrome a few weeks after SARS-COV-2 infection. Vaccines are available to help prevent COVID-19 disease; by August 2021, 7 vaccines had been authorized for use by the WHO to prevent COVID-19 caused by SARS-CoV-2, with others approved by country regulatory authorities.

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2019-nCoV: A Possible Progenitor for SARS-CoV with Bat Origin?

10.20944/preprints202003.0159.v1 ◽

2020 ◽

Author(s):

Yongchang Xu ◽

Leyi Wang ◽

Xu Jia ◽

Youjun Feng

Keyword(s):

Public Health ◽

Respiratory Illness ◽

Public Health Emergency ◽

Evolutionary Origin ◽

Interspecies Transmission ◽

Wuhan City ◽

The Past ◽

Novel Coronavirus ◽

Severe Respiratory Illness

A novel coronavirus (2019-nCoV) that is initially found to trigger human severe respiratory illness in Wuhan City of China, 2019, has been recognized as a public health emergency of international concern. In the past two months, this deadly agent has caused 77,785 cases with 2,666 deaths via rapid person-to-person transmission and reached at least 25 countries. However, its evolutionary origin is poorly understood. Here we show integrative evidence that 2019-nCoV is a possible progenitor for SARS-CoV with bat origin. Our finding underscores the importance of tracing origin in the efficient monitoring, and effectively preventing the interspecies transmission of such emerging/re-emerging coronaviruses.

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Natural compounds as potential inhibitors of novel coronavirus (COVID-19) main protease: An in silico study

10.21203/rs.3.rs-22839/v1 ◽

2020 ◽

Cited By ~ 3

Author(s):

Amaresh Mishra ◽

Yamini Pathak ◽

Vishwas Tripathi

Keyword(s):

In Silico ◽

Structural Diversity ◽

Natural Compounds ◽

Binding Energies ◽

Maslinic Acid ◽

Main Protease ◽

In Silico Studies ◽

Gallocatechin Gallate ◽

Novel Coronavirus ◽

Potential Inhibitors

Abstract COVID-19 pandemic, a novel coronavirus disease is caused by severe acute respiratory syndrome corona virus, SARS-CoV-2. It was first reported in Wuhan, China and has now expanded to more than 190 countries across the world. Till date, there is no specific medication available to prevent or target SARS CoV-2 infection. Very recently, the crystal structure of COVID- 19 main protease (Mpro) was revealed by Liu et al. (2020). SARS-CoV-2 main protease (Mpro) is a key enzyme that plays a crucial role in viral replication and transcription. Thus, Mpro could be a promising target to inhibit SARS-CoV-2 infection. Natural compounds due to their structural diversity and safety are considered as an excellent source of antiviral drugs. In this study, we selected Herbacetin, Rhoifolin, Pectolinarin, Apigenin, Luteolin, Amentoflavone, Daidzein, Puerarin, Epigallocatechin, Gallocatechin gallate, Resveratrol, Maslinic acid, Piperine and Ganomycin B to target the SARS-CoV-2 main protease (Mpro) using in silico tools. These compounds were examined based on ADME, drug likeness, docking studies, MD simulations using CABS-flex 2.0, and prediction of major toxicity parameters (hepatotoxicity & cytotoxicity) to check the safety aspects of the selected compounds. We also investigated the similarity of these compounds, if any, with FDA approved drugs using Swiss similarity. The docking results were found in the order of Amentoflavone (-9.13 kcal/mol), Ritonavir (-8.52 kcal/mol), Lopinavir (-8.5 kcal/mol), Puerarin (-7.97 kcal/mol), Maslinic acid (-7.97 kcal/mol), Piperine (-7.65 kcal/mol), Gallocatechin gallate (-7.59 kcal/mol), Luteolin (-7.58 kcal/mol), Apigenin (-7.42 kcal/mol), Resveratrol (-7.41 kcal/mol), Herbacetin (-7.4 kcal/mol), Daidzein (-7.32 kcal/mol), Rhoifolin (-6.71 kcal/mol), Ganomycin B (-6.46 kcal/mol), Epigallocatechin (-6.13 kcal/mol), and Pectolinarin (-5.88 kcal/mol). Among these selected natural compounds, Amentoflavone and Puerarin were the two top leads which showed the lowest binding energies. Interestingly, Amentoflavone showed highest binding affinity among all the selected compounds. Our promising findings based on in-silico studies warrants further clinical trial in order to use these compounds as potential inhibitors of SARS-CoV-2 protease.

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Natural Products with tandem Anti-inflammatory, Immunomodulatory and Anti-SARS-CoV/2 effects: A Drug Discovery Perspective against SARS-CoV-2

Current Medicinal Chemistry ◽

10.2174/0929867328666210726094955 ◽

2021 ◽

Vol 28 ◽

Author(s):

Luana N. O. Leal da Cunha ◽

Tiago Tizziani ◽

Gabriella B. Souza ◽

Monalisa A. Moreira ◽

José S. S. Neto ◽

...

Keyword(s):

Natural Products ◽

Drug Discovery ◽

In Silico ◽

Biological Activities ◽

Cysteine Proteases ◽

Drug Candidate ◽

Plant Metabolites ◽

Drug Candidates ◽

In Silico Studies ◽

Anti Inflammatory

Background: COVID-19 is still causing victims with long-term health consequences, mass deaths, and collapsing healthcare systems around the world. The disease has no efficient drugs. However, previous studies revealed that SARS-CoV-2 and SARS-CoV have 96% and 86.5% similarities in cysteine proteases (3CLpro) and papain-like protease (PLpro) sequences, respectively. This resemblance could be significant in the search for drug candidates with antiviral effects against SARS-CoV-2. Objective: This paper is a compilation of natural products that inhibit SARS-CoV 3CLpro and PLpro and, concomitantly, reduce inflammation and/or modulate the immune system as a perspective strategy for COVID-19 drug discovery. It also presents in silico studies performed on these selected natural products using SARS-CoV-2 3CLpro and PLpro as targets to propose a list of hit compounds. Method: The plant metabolites were selected in the literature based on their biological activities on SARS-CoV proteins, inflammatory mediators, and immune response. The consensus docking analysis was performed using four different packages. Results: Seventy-nine compounds reported in the literature with inhibitory effects on SARS-CoV proteins were reported as anti-inflammatory agents. Fourteen of them showed in previous studies immunomodulatory effects. Five and six of these compounds showed significant in silico consensus as drug candidates that can inhibit PLpro and 3CLpro, respectively. Our findings corroborated recent results reported on anti-SARS-CoV-2 in the literature. Conclusion: This study revealed that amentoflavone, rubranoside B, savinin, psoralidin, hirsutenone, and papyriflavonol A are good drug candidate for the search of antibiotics against COVID-19.

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