scholarly journals From Wuhan to COVID-19 Pandemic: An Up-to-Date Review of Its Pathogenesis, Potential Therapeutics, and Recent Advances

2020 ◽  
Vol 8 (6) ◽  
pp. 850 ◽  
Author(s):  
Ikrame Zeouk ◽  
Khadija Bekhti ◽  
Jacob Lorenzo-Morales
Keyword(s):  
Antiviral Agents ◽  
Pathogen Inactivation ◽  
Life Threatening ◽  
Antiparasitic Drugs ◽  
Asymptomatic Individuals ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Tract Infections ◽  
Fda Approved Drugs ◽  
Screening Approaches

The emergence of a novel human coronavirus (SARS-CoV-2) causing severe contagious respiratory tract infections presents a serious threat to public health worldwide. To date, there are no specific antiviral agents available for this disease, currently known as COVID-19. Therefore, genomic sequencing and therapeutic clinical trials are being conducted to develop effective antiviral agents. Several reports have investigated FDA-approved drugs as well as in silico virtual screening approaches such as molecular docking and modeling to find novel antiviral agents. Until now, antiparasitic drugs such as chloroquine have shown the most relevant results. Furthermore, there is an urgent need to understand the pathogenesis of this novel coronavirus, its transmission routes, surface survival and evolution in the environment. So far, the scientific community has indicated a possible transmission of COVID-19 via blood transfusion which is challenging in the case of asymptomatic individuals. Protocols for pathogen inactivation are also needed. In this paper, we reviewed recent findings about this life-threatening pandemic.

scholarly journals Combinatorial therapeutic plan for COVID-19 treatment armed up with antiviral, antiparasitic, cell-entry inhibitor, and immune-boosters

2020 ◽  
Author(s):  
Nabanita Roy Chattopadhyay ◽  
Koustav Chatterjee ◽  
Antara Banerjee ◽  
Tathagata Choudhuri
Keyword(s):  
Cell Entry ◽  
Entry Inhibitor ◽  
Time Loss ◽  
Antiparasitic Drug ◽  
A Cell ◽  
Host Cell Entry ◽  
Antiparasitic Drugs ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract SARS-CoV-2, or novel coronavirus, is causing the fatal and contagious coronavirus disease-2019 (COVID-19) affecting thousands of people every single day. Researchers are continuously searching for any possible cure and/or vaccine, but no conclusive report is available till date. Like many others, we realize that a rapid, immediate, and elaborate strategy must be adopted to protect mankind. To avoid the time-loss due to clinical trials, we have tested some FDA-approved drugs to combat COVID-19. We accessed information from public databases and publications, and studied the mechanism of infection of SARS-CoV-2 and the interactions of various drugs with SARS-CoV-2 proteins in silico. We found a few antivirals and antiparasitic drugs to interact with important SARS-CoV-2 proteins. Particularly Galidesivir, Remdesivir, and Pirodavir are the chosen antiviral drugs; and Proguanil, Mefloquine, and Artesunate are the chosen antiparasitic drugs. In addition, inhibitors to prevent host-cell entry and a few supportive immuneboosters can be used in different combinations. Our study proposes a four-way attack to this fatal virus for the possible management of COVID-19 armed up with an antiviral, an antiparasitic drug, a cell-entry inhibitor, and a few supportive immune-boosters, which can be used in different combinations in different groups of people.

SARS-COV2 virus and Coronavirus disease (COVID-19)

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 977-982
Author(s):  
Mohamed J. Saadh ◽  
Bashar Haj Rashid M ◽  
Roa’a Matar ◽  
Sajeda Riyad Aldibs ◽  
Hala Sbaih ◽  
...  
Keyword(s):  
Close Contact ◽  
Antiviral Agents ◽  
Health Concern ◽  
The Novel ◽  
Global Public Health ◽  
Fatal Disease ◽  
Mild Disease ◽  
Life Threatening ◽  
Novel Coronavirus

SARS-COV2 virus causes Coronavirus disease (COVID-19) and represents the causative agent of a potentially fatal disease that is of great global public health concern. The novel coronavirus (2019) was discovered in 2019 in Wuhan, the market of the wet animal, China with viral pneumonia cases and is life-threatening. Today, WHO announces COVID-19 outbreak as a pandemic. COVID-19 is likely to be zoonotic. It is transmitted from bats as intermediary animals to human. Also, the virus is transmitted from human to human who is in close contact with others. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is nearly supportive; the role of antiviral agents is yet to be established. The SARS-COV2 virus spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. In this article, we aimed to summarize the transmission, symptoms, pathogenesis, diagnosis, treatment, and vaccine to control the spread of this fatal disease.

scholarly journals Repurposing of FDA Approved Drugs for the Identification of Potential Inhibitors of SARS-CoV-2 Main Protease

2020 ◽  
Author(s):  
Abhik Kumar Ray ◽  
Parth Sarthi Sen Gupta ◽  
Saroj Kumar Panda ◽  
Satyaranjan Biswal ◽  
Malay Kumar Rana
Keyword(s):  
Virtual Screening ◽  
Binding Energies ◽  
Great Promise ◽  
Main Protease ◽  
Promising Target ◽  
Inhibitory Potential ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Potential Inhibitors ◽  
Fda Approved Drugs

<p>COVID-19, responsible for several deaths, demands a cumulative effort of scientists worldwide to curb the pandemic. The main protease, responsible for the cleavage of the polyprotein and formation of replication complex in virus, is considered as a promising target for the development of potential inhibitors to treat the novel coronavirus. The effectiveness of FDA approved drugs targeting the main protease in previous SARS-COV (s) reported earlier indicates the chances of success for the repurposing of FDA drugs against SARS-COV-2. Therefore, in this study, molecular docking and virtual screening of FDA approved drugs, primarily of three categories: antiviral, antimalarial, and peptide, are carried out to investigate their inhibitory potential against the main protease. Virtual screening has identified 53 FDA drugs on the basis of their binding energies (< -7.0 kcal/mol), out of which the top two drugs Velpatasvir (-9.1 kcal/mol) and Glecaprevir (-9.0 kcal/mol) seem to have great promise. These drugs have a stronger affinity to the SARS-CoV-2 main protease than the crystal bound inhibitor α-ketoamide 13B (-6.7 kcal/mol) or Indinavir (-7.5 kcal/mol) that has been proposed in a recent study as one of the best drugs for SARS-CoV-2. The <i>in-silico</i> efficacies of the screened drugs could be instructive for further biochemical and structural investigation for repurposing. The molecular dynamics studies on the shortlisted drugs are underway. </p>

scholarly journals Evaluation of Yashtimadhu (Glycyrrhiza glabra) active Phytochemicals Against Novel Coronavirus (SARS-CoV-2)

2020 ◽  
Author(s):  
Dharmendra Kumar Maurya
Keyword(s):  
Viral Entry ◽  
Virus Disease ◽  
Scientific Basis ◽  
Docking Studies ◽  
Angiotensin Converting Enzyme 2 ◽  
Main Protease ◽  
Docking Approach ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract Corona Virus Disease 2019 (COVID-19) caused by a novel coronavirus emerged from Wuhan, China in December 2019. It has spread to more than 205 countries and become pandemic now. Currently, there are no FDA approved drugs or vaccines available and hence several studies are going on in search of suitable drug that can target viral proteins or host receptor for the prevention and management of COVID-19. The search for plant-based anti-viral agents against the SARS-CoV-2 is promising because several of plants have been shown to possess anti-viral activities against different viruses. Here, we used molecular docking approach to explore the use of Indian Ayurvedic herbs, Yashtimadhu in prevention and management of COVID-19. In the present study we have evaluated the effectiveness of phytochemicals found in Yashtimadhu against Main Protease (Mpro), Spike (S) protein and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 as well as human angiotensin converting enzyme 2 (ACE2) receptor and furin protease. Apart from this, we have also performed in-silico drug-likeness and predicted pharmacokinetics of the selected phytochemicals found in the Yashtimadhu. Our study shows that several phytochemicals found in this plant have potential to bind with important proteins of SARS-CoV-2 which are essential for viral infection and replication. Overall our study provides scientific basis in terms of binding of active ingredients present in Yashtimadhu with SARS-CoV-2 target proteins. Our docking studies reveal that Yashtimadhu may inhibit the viral severity by interfering with viral entry as well as its multiplication in the infected persons. Thus Yashtimadhu may be helpful in the prevention and management of the COVID-19.

scholarly journals Potential Inhibitors Against Papain-like Protease of Novel Coronavirus (COVID-19) from FDA Approved Drugs

2020 ◽  
Author(s):  
Rimanshee Arya ◽  
Amit Das ◽  
Vishal Prashar ◽  
Mukesh Kumar
Keyword(s):  
Life Cycle ◽  
Active Site ◽  
Homology Model ◽  
Docking Studies ◽  
Rational Selection ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Potential Inhibitors ◽  
Fda Approved Drugs ◽  
Selection Of

<p>The cases of 2019 novel coronavirus (COVID-19) infection have been continuously increasing ever since its outbreak in China last December. Currently, there are no approved drugs to treat the infection. In this scenario, there is a need to utilize the existing repertoire of FDA approved drugs to treat the disease. The rational selection of these drugs could be made by testing their ability to inhibit any COVID-19 proteins essential for viral life-cycle. We chose one such crucial viral protein, the papain-like protease (PLpro), to screen the FDA approved drugs <i>in silico</i>. The homology model of the protease was built based on the SARS-coronavirus PLpro structure, and the drugs were docked in S3/S4 pockets of the active site of the enzyme. In our docking studies, fifteen FDA approved drugs, including chloroquine and formoterol, bind the target enzyme with significant affinity and good geometry, suggesting their potential to be utilized against the virus.</p>

scholarly journals Advanced Bioinformatics Rapidly Identifies Existing Therapeutics for Patients with Coronavirus Disease - 2019 (COVID-19)

2020 ◽  
Author(s):  
Jason Kim ◽  
Jenny zhang ◽  
Yoonjeong Cha ◽  
Sarah Kolitz ◽  
Jason Funt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Potential Benefit ◽  
Expression Patterns ◽  
Antiviral Agents ◽  
Protective Effects ◽  
Beta Lactam ◽  
Global Pandemic ◽  
Lactam Antibiotic ◽  
Approved Drugs ◽  
Fda Approved Drugs

<p>The recent global pandemic has placed a high priority on identifying drugs to prevent or lessen clinical infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused by Coronavirus disease – 2019 (COVID-19). We applied two computational approaches to identify potential therapeutics. First, we sought to identify existing FDA approved drugs that could block coronaviruses from entering cells by binding to ACE2 or TMPRSS2 using a high-throughput AI-based binding affinity prediction platform. Top results included several ACE inhibitors, a beta-lactam antibiotic, two antiviral agents (Fosamprenavir and Emricasan) and glutathione. The platform also assessed specificity for ACE2 over ACE1, important for avoiding counterregulatory effects. Further studies are needed to weigh the benefit of blocking virus entry against potential counterregulatory effects and possible protective effects of ACE2. However, the data herein suggest readily available drugs that warrant experimental evaluation to assess potential benefit. Second, we sought to identify FDA approved drugs that could attenuate the gene expression patterns induced by coronaviruses, using our Disease Cancelling Technology (DCT) platform. DCT was run on an animal model of SARS-CoV, and ranked compounds by their ability to induce gene expression signals that counteract disease-associated signals. Top hits included Vitamin E, ruxolitinib, and glutamine. Glutathione and its precursor glutamine were highly ranked by two independent methods, suggesting both warrant further investigation for potential benefit against SARS-CoV-2. While these findings are not yet ready for clinical translation, this report highlights the potential use of two bioinformatics technologies to rapidly discover existing therapeutic agents that warrant further investigation for established and emerging disease processes.</p>

scholarly journals Virtual Screening Enabled Selection of Antiviral Agents Against Covid-19 Disease Targeting Coronavirus Endoribonuclease NendoU: Plausible Mechanistic Interventions in the Treatment of New Virus Strain

2020 ◽  
Author(s):  
Gaurav Joshi ◽  
Ramarao Poduri
Keyword(s):  
Virtual Screening ◽  
Homo Sapiens ◽  
Antiviral Agents ◽  
Drug Repurposing ◽  
Experimental Drugs ◽  
Experimental Drug ◽  
Investigational Drugs ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Selection Of

<p>SARS-CoV-2 is the seventh coronavirus that is reported to cause infection in Homo sapiens. Considering its pandemic nature, development of newer and effective therapeutic strategies, drug repurposing in combination with target validation approaches has led to the identification of new antiviral molecules. In current work, we performed virtual screening and molecular docking of 8548 ligands on target protein coronavirus endoribonuclease NendoU (3VWW). The molecules selected includes FDA approved drugs along with investigational or experimental drugs recommended for anticancer, antiviral, antimicrobial, and antiprotozoal properties. The thorough selection and their rationality with Covid-19 led us to propose that FDA approved drug DB00876 (Eprosartan), Investigational drugs DB15063 (Inarigivir soproxil), DB12307 (Foretinib) and DB01813 an experimental drug may be repurposed for treatment of Covid-19 disease.</p>

scholarly journals Protoporphyrin IX and verteporfin prevent SARS-CoV-2 infection in vitro and in a mouse model expressing human ACE2

2020 ◽  
Author(s):  
Chenjian Gu ◽  
Yang Wu ◽  
Huimin Guo ◽  
Yuanfei Zhu ◽  
Wei Xu ◽  
...  
Keyword(s):  
Cytopathic Effect ◽  
Antiviral Agents ◽  
Protoporphyrin Ix ◽  
Ring Structure ◽  
Receptor Binding Domain ◽  
Viral Receptor ◽  
Margin Of Safety ◽  
Approved Drugs ◽  
Fda Approved Drugs

AbstractThe SARS-CoV-2 infection is spreading rapidly worldwide. Efficacious antiviral therapeutics against SARS-CoV-2 is urgently needed. Here, we discovered that protoporphyrin IX (PpIX) and verteporfin, two FDA-approved drugs, completely inhibited the cytopathic effect produced by SARS-CoV-2 infection at 1.25 μM and 0.31 μM respectively, and their EC50 values of reduction of viral RNA were at nanomolar concentrations. The selectivity indices of PpIX and verteporfin were 952.74 and 368.93, respectively, suggesting broad margin of safety. Importantly, PpIX and verteporfin prevented SARS-CoV-2 infection in mice adenovirally transduced with human ACE2. The compounds, sharing a porphyrin ring structure, were shown to bind viral receptor ACE2 and interfere with the interaction between ACE2 and the receptor-binding domain of viral S protein. Our study suggests that PpIX and verteporfin are potent antiviral agents against SARS-CoV-2 infection and sheds new light on developing novel chemoprophylaxis and chemotherapy against SARS-CoV-2.

Drug discovery of small molecules for the treatment of COVID-19: A review on clinical studies

2020 ◽  
Vol 21 ◽  
Author(s):  
Bharat Goel ◽  
Nivedita Bhardwaj ◽  
Nancy Tripathi ◽  
Shreyans K. Jain
Keyword(s):  
Small Molecules ◽  
Clinical Studies ◽  
Ebola Virus ◽  
Viral Infections ◽  
New Drugs ◽  
Zoonotic Virus ◽  
Traditional Medicines ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Fda Approved Drugs

: Recently, a sudden outbreak of novel coronavirus disease (COVID-19) was caused by a zoonotic virus known as severe acute respiratory syndrome coronavirus (SARS-CoV-2). It has caused pandemic situations around the globe and affecting the lives of millions of people. So far, no drug has been approved for the treatment of SARS-CoV-2 infected patients. As of now, more than 1000 clinical trials are going on for repurposing of FDA approved drugs and for evaluating the safety & efficiency of experimental antiviral molecules to combat COVID-19. Since the development of new drugs may require months to years to reach the market, this review focusses on the potentials of existing small molecule FDA approved drugs and the molecules already in the clinical pipeline against viral infections like HIV, hepatitis B, Ebola virus, and other viruses of coronavirus family (SARS-CoV and MERS-CoV). The review also discusses the natural products and traditional medicines in clinical studies against COVID-19. Currently, 1978 studies are active, 143 completed and 4 posted results (as on June 13, 2020) on clinicaltrials.gov.

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