Systematic structure guided clustering of chemical lead compounds targeting RdRp of SARS-CoV-2

BACKGROUND: To combat the global health issue caused by SARS-CoV2, scientists are attempting various therapeutic approaches towards drug discovery including computational biology and drug-repurposing. Recent studies have highlighted the conserved nature of RNA-dependent RNA polymerase (RdRp) of coronaviruses affecting human, bat and animals. In this study attempts have been made to identify the potential inhibitors of RdRp by utilizing molecular docking and MD simulation studies. METHOD(S): Systematic structure-based screening of chemical compounds from public libraries was performed to identify the potential lead molecules inhibiting RdRp. This structure driven clustering of compounds is based on decision tree model generated by combining two properties: 1) shape descriptors;and 2) critical number of multiple bonds. The enabled screening of potential chemical compounds was subjected to molecular docking followed by molecular dynamics simulation studies. RESULT(S): The results revealed that the stability of protein-drug complex structure was in the order of RdRp-Oxoglaucine >RdRp-Flutroline >RdRp-Brucine complex. CONCLUSION(S): This study identifies Oxoglaucine, Brucine and Flutroline as prospective inhibiting agents of SARS-CoV-2 RdRp and further warrants for experimental validation. Copyright © 2022 EDIZIONI MINERVA MEDICA.

Variants of SARS-CoV-2, their effects on infection, transmission and neutralization by vaccine-induced antibodies.

OBJECTIVE: The current study reviewed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) variants for their effects on infection, transmission and neutralization by vaccine-induced antibodies. MATERIALS AND METHODS: The research articles for the current study were searched over PubMed, Google Scholar, EMBASE and Web of Science online databases. The keywords used were: (("SARS-CoV-2" OR "COVID-19") AND ("mutation" OR "variant") AND ("death" OR "hospitalization" OR "infection" OR "transmission") AND ("antibody" OR "neutralize" OR "vaccine")). A total of 333 research articles were retrieved through online-database search. These articles were further scrutinized for their relevancy. Additionally, searches were performed to find the latest relevant information over Google search engine and relevant news browsers. Finally, around 35 germane articles were considered for scripting the current report. RESULTS: The mutations have changed amino acids at key positions in spike protein viz. S477N, E484K, Q677H, E484Q, L452R, K417T, K417N and N501Y. These mutations are relevant for different characteristics and are present in newly evolved strains of SARS-CoV-2 like E484K in B.1.526, B.1.525, P.2, B.1.1.7, P.1 and B.1.351. Mutations have increased the immune escape potential leading to 3.5-6.5-folds decrease in neutralization of antibodies (Pfizer and Moderna vaccines). The variant, B.1.617 circulating in India and many other countries (double variant) having E484Q and L452R mutations, has raised the infection rate and decreased the neutralization capacity of the vaccine-induced antibodies. Deadly K417N+E484K+N501Y triplet mutations found in B.1.351 and P.1 have increased the transmission ability of these strains by 50% leading to greater COVID-19 hospitalization, ICU admissions and deaths. CONCLUSIONS: The new SARS-CoV-2 variants have compromised the neutralization potential of the currently used vaccines, but still, they have considerable efficacy to reduce infection and mortality. GRAPHICAL ABSTRACT: https://www.europeanreview.org/wp/wp-content/uploads/Graphical_Abstract.jpg.

Positive and negative effects of COVID-19 pandemic on aquatic environment: A review

In December 2019, a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak was reported for the first time in Wuhan, Hubei province, China. This coronavirus has been referred as Coronavirus Disease 2019 or COVID-19 by World Health Organization (WHO). The spread of COVID-19 has become unstoppable, infecting around 93.5 million people worldwide, with the infections and deaths still increasing. Today, the entire planet has changed due to the greatest threat on the planet since the introduction of this lethal disease. This pandemic has left the world in turmoil and various measures have been taken by many countries including movement control order or lockdown, to slow down or mitigate the infection. Since the lockdown has been implemented almost in all affected countries, there has been a significant reduction in anthropogenic activity, including a reduction in industrial operations, vehicle numbers, and marine-related activities. All of these changes have also led to some unexpected environmental consequences. As a result of this lockdown, it had a positive and negative impact on the environment including the aquatic environment. Hence this review will therefore focus on the good and bad perspectives of the lockdown toward the aquatic environment. © 2021 Penerbit Universiti Kebangsaan Malaysia. All rights reserved.

SARS CoV, MERS CoV, SARS CoV-2 and treatments: A bibliometric analysis

As the incidences of Coronavirus (SARS CoV-2) infections have been increasing at a rapid pace, the need for its containment and treatment has taken center stage for numerous research institutions. The similarity of SARS CoV-2 with that of SARS CoV has led to a jumpstart in the research activities on coronavirus on the same. The number of research articles appearing since the time SARS CoV-2 was discovered has skyrocketed. While every research group has been busy in pushing the research information to the next level, hardly any convincing research has come up the effective treatments or therapeutics against the disease. In this study we conduct a bibliographic analysis for SARS CoV, MERS CoV and SARS CoV-2, and statistically compare the incidence of research articles combining along the “treatment” and „therapies” as keywords. We attempt to draw trends and conclusions based on the data available on the databases mined.

Impact of COVID-19 on the cerebrovascular system and the prevention of RBC lysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) uses Angiotensin- converting enzyme 2 (ACE2) receptors to infect host cells which may lead to coronavirus disease (COVID-19). Given the presence of ACE2 receptors in the brain and the critical role of the renin-angiotensin system (RAS) in brain functions, special attention to brain microcirculation and neuronal inflammation is warranted during COVID-19 treatment. Neurological complications reported among COVID-19 patients range from mild dizziness, headache, hypogeusia, hyposmia to severe like encephalopathy, stroke, Guillain-Barre Syndrome (GBS), CNS demyelination, infarcts, microhemorrhages and nerve root enhancement. The pathophysiology of these complications is likely via direct viral infection of the CNS and PNS tissue or through indirect effects including post- viral autoimmune response, neurological consequences of sepsis, hyperpyrexia, hypoxia and hypercoagulability among critically ill COVID-19 patients. Further, decreased deformability of red blood cells (RBC) may be contributing to inflammatory conditions and hypoxia in COVID-19 patients. Haptoglobin, hemopexin, heme oxygenase-1 and acetaminophen may be used to maintain the integrity of the RBC membrane.