Vulnerabilities of the SARS-CoV-2 Virus to Proteotoxicity —Opportunity for Repurposed Chemotherapy of COVID-19 Infection

The global pandemic of COVID-19 disease caused by infection with the SARS-CoV-2 coronavirus, has produced an urgent requirement and search for improved treatments while effective vaccines are developed. A strategy for improved drug therapy is to increase levels of endogenous reactive metabolites for selective toxicity to SARS-CoV-2 by preferential damage to the viral proteome. Key reactive metabolites producing major quantitative damage to the proteome in physiological systems are: reactive oxygen species (ROS) and the reactive glycating agent methylglyoxal (MG); cysteine residues and arginine residues are their most susceptible targets, respectively. From sequenced-based prediction of the SARS-CoV-2 proteome, we found 0.8-fold enrichment or depletion of cysteine residues in functional domains of the viral proteome; whereas there was a 4.6-fold enrichment of arginine residues, suggesting SARS-CoV-2 is resistant to oxidative agents and sensitive to MG. For arginine residues of the SARS-CoV-2 coronavirus predicted to be in functional domains, we examined which are activated toward modification by MG – residues with predicted or expected low pKa by neighboring group in interactions. We found 25 such arginine residues, including 2 in the spike protein and 10 in the nucleoprotein. These sites were partially conserved in related coronaviridae: SARS-CoV and MERS. Finally, we identified drugs which increase cellular MG concentration to virucidal levels: antitumor drugs with his...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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Authors: Schwartz RA, Sharma A, Szepietowski JC, Sandhu S, Goldust M Abstract Early December 2019 witnessed an international outbreak of a novel coronavirus (COVID 19) designated severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Since then, a number of therapeutic molecules have been explored to have potential efficacy against the SARS-Cov-2 per se or its sequelae. There are no Food and Drug Administration specific therapies approved so far; however, numerous drugs based on varying levels of evidence, in vitro studies and compassionate drug trials are being established as therapeutic agents, especially ...
Source: Journal of Drugs in Dermatology - Category: Dermatology Tags: J Drugs Dermatol Source Type: research
Coronavirus (CoV) outbreaks have recently emerged as a global public health threat due to their exceptional zoonotic potential — a feature arising from their ability to infect a diverse range of potential hosts combined with their high capacity for mutation and recombination. After Severe Acute Respiratory Syndrome (SARS) CoV-1 in 2003 and Middle East Respiratory Syndrome (MERS) CoV in 2012, with the current SARS-CoV-2 pandemic we are now in the midst of the third deadly international CoV outbreak in less than 20 years. Coronavirus outbreaks present a critical threat to global public health and an urgent necessity fo...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Covid-19 is a recently-emerged infectious disease caused by the novel severe acute respiratory syndrome coronavirus SARS-CoV2. SARS-CoV2 differs from previous coronavirus infections (SARS and MERS) due to its high infectivity (reproduction value, R0, typically 2–4) and pre- or asymptomatic transmission, properties that have contributed to the current global Covid-19 pandemic. Identified risk factors for disease severity and death from SARS-Cov2 infection include older age, male sex, diabetes, obesity and hypertension. The reasons for these associations are still largely obscure. Evidence is also emerging that SARS-Co...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Tony Schountz joins TWiV to explain the work of his laboratory showing that deer mice can be infected with and transmit SARS-CoV-2, and how his colony of Jamaican fruit bats is being used to understand their response to virus infections.
Source: virology blog - Category: Virology Authors: Tags: This Week in Virology coronavirus COVID-19 deer mouse fruit bat hantavirus MERS-CoV pandemic reservoir host SARS-CoV-2 viral viruses zoonosis Source Type: blogs
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 infection has recently spread worldwide was declared a pandemic on March 11. The most common symptoms of COVID-19 disease are fever, fatigue, and dry cough. Some patients may experience pain and aches, nasal congestion, cold, sore throat or diarrhea. These symptoms are usually mild and begin gradually. Currently, the source of the virus is still unknown. However, all available evidence indicates that the origin of this virus is a natural animal and that it is not a manufactured virus. The virus spreads faster than ...
Source: Reviews in Medical Microbiology - Category: Microbiology Tags: VIROLOGY Source Type: research
This study provides useful insights for the identification of potential non-pathogenic (to humans) surrogates to understand inactivation kinetics and their use in experimental validation of UV-C disinfection systems. This approach can be used to narrow the number of surrogates used in testing UV-C inactivation of other human and animal ssRNA viral pathogens for experimental validation that can save cost, labor and time.
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
This report aims to highlight Resveratrol as possible therapeutic candidate in SARS-CoV-2 infection. The antiviral efficacy of Resveratrol was demonstrated for several viruses, including coronavirus. Resveratrol was shown to mitigate the major pathways involved in the pathogenesis of SARS-CoV-2, including regulation of the renin-angiotensin system (RAS) and expression of angiotensin-converting enzyme 2 (ACE2), stimulation of immune system and downregulation of pro-inflammatory cytokines release. It was also reported to promote SIRT1 and p53 signaling pathways and increase cytotoxic T lymphocytes (CTLs) and natural kil...
Source: Acta Virologica - Category: Infectious Diseases Authors: Tags: Acta Virol Source Type: research
The recent pandemic of coronavirus infectious illness 2019 (COVID19) triggered by SARS-CoV-2 has rapidly spread around the globe, generating in severe events an acute, highly lethal pneumonia and death. In the past two hitherto similar CoVs, the severe acute respiratory syndrome CoV (SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV) also gained universal attention as they produced clinical symptoms similar to those of SARS-CoV-2 utilizing angiotensin-converting enzyme 2 (ACE2) receptor and dipeptidyl peptidase 4 (DPP4) to go into the cells. COVID-19 may also present with overtly neurological symptoms. The pro...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Abstract The World Health Organization (WHO) recognized a novel coronavirus as the causative agent of a new form of pneumonia. It was subsequently named COVID-19 and reported as the source of a respiratory disease occurrence starting in December 2019 in Wuhan, Hubei Province, China. It has been affirmed a public health emergency of international significance by the World Health Organization. It is regarded as a subset of the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS); COVID-19 is triggered by a betacoronavirus called SARS-CoV-2, which affects the lower respiratory trac...
Source: Environmental Science and Pollution Research International - Category: Environmental Health Authors: Tags: Environ Sci Pollut Res Int Source Type: research
Abstract The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) recently caused a pandemic outbreak called coronavirus disease 2019 (COVID-19). This disease has initially been reported in China and also now it is expeditiously spreading around the globe directly among individuals through coughing and sneezing. Since it is a newly emerging viral disease and obviously there is a lack of anti-SARS-CoV-2 therapeutic agents, it is urgently required to develop an effective anti-SARS-CoV-2-agent.Through recent advancements in computational biology and biological assays, several natural compounds and their deriv...
Source: Virus Research - Category: Virology Authors: Tags: Virus Res Source Type: research
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