Coronaviruses - Volume 2, Issue 11, 2021

Older adults are at a higher risk of developing serious illness and mortality from COVID-19. Among a multitude of factors, cellular senescence associated with ageing, obesity, cardiovascular diseases, and diabetes seems to be statistically correlated with severe SARS-CoV-2 infections and mortality. Surface proteins such as vimentin and CD26 that are differentially expressed on senescent cells seem important for SARS-CoV-2 attachment and internalization. Potential therapeutic agents against this novel virus also exhibit senolytic and anti-inflammatory actions, implicating that their beneficial effects could, in part, be attributed to their senescent cell removal and the associated inflammatory phenotype neutralizing properties. Elucidating the underlying molecular mechanisms that connect cellular senescence and severity of SARS-CoV-2 infection might help direct towards development of effective therapeutics for elderly patients of COVID-19.

The clinical outcomes of COVID-19 patients highlight a significant minority of subjects with very rapid lethal outcomes subsequent to the almost complete healing after coronavirus infections for most of the subjects involved. In addition, the reckless use of some drugs and therapeutic protocols that have not shown any efficacy in reducing mortality in those patients where the progression of the disease was unstoppable suggests a different interpretative model in the pathogenesis of severe cases. Starting from the clinical data already known for almost twenty years on the behavior of human SARS coronaviruses, it is possible to develop a new hypothesis. The reference points taken into consideration are: i) the comparison of the histological evidence of the autoptic material; ii) the poor pharmacological response in subjects with severe phenotypes of the pathology; iii) the common element of endotheliitis in a subgroup of the population characterized by harmful clinical outcomes during the evolution of the pathology. The tendency to develop widespread, massive endothelial lesions not responding to any drug therapy or other interventions necessarily plays a crucial role in the onset of the systemic and severe stage of the disease. The present perspective opens the door to a different therapeutic approach both to the full-blown phase of COVID-19 and to the preventive phase or the very first manifestations of the disease. It is imperative to pay more attention to the protection of the vascular endothelium in subjects who already have a predisposition to the development of a severe evolution of this ailment rather than to give a simple antiviral therapy together with symptomatic drugs.

COVID-19 pandemic affected over 227 countries with more than 147 million infections that claimed 31.22 lacs lives. The first case of the pandemic was reported from China in Dec, 2019 showing pneumonia like symptoms that turned out to be the novel strain of coronavirus (2019-n- CoV). The WHO declared 2019-nCoV infection as the Public Health Emergency of International Concern and the disease named coronavirus disease (COVID-19). The infection curve of the pandemic has been flattened in many countries around the world, but the effective new antiviral drugs or vaccine has not yet developed. So far, we are saved by non-pharmaceutical interventions like handwashing, social distancing, quarantine, masks and health-care workers by personal protective equipments. Now the question arises that what we do if no effective drug or vaccine emerges? In the absence of effective drug/vaccines, pandemic has to be fought at community level not at hospitals. For such emergent situations, we need a ‘Plan B’ based non-vaccine/drug interventions.

A century after the outbreak of the Spanish flu, the world is suffering from another pandemic because of the coronavirus. The virus took a toll on more than millions of lives worldwide and continues to affect the health and socio-economic infrastructure all over the world. This study explores the epidemiology, etiology, and transmission of the virus and its phylogenetic relationship with SARS and MERS coronavirus responsible for the 2002 and 2012 viral outbreak. Furthermore, this review highlights the key features of the viral genome and essential viral proteins responsible for the viral life cycle, evading host immune response, and viral immunopathology with therapeutics from “Recovery” and “Solidarity” trials. The review culminates with a discussion on different classes of prominent vaccines and their efficacy. An overall understanding of essential viral proteins and their role in pathogenesis, repurposed drugs, and vaccine development is the rationale of the present review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus and then transmitted to a human at Wuhan city of China. On February 11, 2020, the WHO announced a name for the new coronavirus disease as COVID-19. Finally, the WHO declared the novel coronavirus outbreak a global pandemic on March 11, 2020. Within a few months, SARS-CoV-2 had spread across the world to 220 countries, areas or territories. The main objective of this work is to review the existing knowledge about COVID-19, its updated status, available treatment procedures and future challenges. The available literature based on the COVID-19 was thoroughly reviewed and concise, evidence-based information was explored for the public interest. Various authentic databases like PubMed, Scopus, and Google Scholar together with the official sites of some Govt. Organizations were carefully searched for all relevant information about the current status of COVID-19, including the published research on coronavirus. More than 68 million people are already infected, including around 20% severely ill, with almost 1.5 million casualties due to this virus which is expected to infect approximately 70% population worldwide. Currently, maximum confirmed cases and death are reported in the USA. The epicentre of the pandemic was initially shifted from China to Europe, then to the USA, Brazil and now India. In between, the understanding of pathogenesis and mode of transmission has been developed; repurposing drugs are being validated and the development of a new vaccine is underway. The study concludes that there is no established treatment available for COVID-19, although 26 clinical and 139 preclinical trials are underway to develop vaccines globally. Although three vaccines are at the advanced stage of development, their efficacy and adverse effects are yet to be validated and recorded. Recently, the Pfizer vaccine has been started for vaccination in emergency cases in England and Bahrain, and the United States of America will start it soon. Meanwhile, prevention, rigorous global containment and quarantine efforts are practiced worldwide to control its spread.

Since the start of the decade, the coronavirus disease 2019 [COVID-19] pandemic has disrupted the world's healthcare system. Scientists have been engaged to bring about a therapeutic agent to help combat the dreaded disease. Many researchers have shown antivirals such as Remdesivir and Favipiravir to be effective in the treatment; however, these drugs have a short half-life. Hence, the need for a drug delivery system that could prolong or alter their effect by increasing the potency of antivirals or vaccines has been proposed. Nanotechnology has always been at the forefront of developing and diagnosing diseases. The idea of which can be borrowed to treat the novel coronavirus. The applicability needs to be vast as the disease has spread, and a fast, reliable, effective therapeutic and diagnostic procedure is the need of the hour. Emphasis on nanotechnology usage through the intranasal and pulmonary route has been given and various applications have also been discussed in this review.

COVID-19 is currently threatening the globe. SARS-CoV-2 is the cause of COVID-19, which spreads via droplets/airborne and direct contact. Health care workers (HCWs) are the frontline workers, which are directly involved in taking care of patients affected by COVID-19. HCWs are at a higher risk of infection during the caring of COVID-19 patients. This focused review highlighted the higher risk for COVID-19 infection among health care professionals during close contact with patients and their preventive management in COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an etiologic agent of the respiratory disease in humans known as coronavirus disease 2019 (COVID-19). The beginning of the outbreak of the disease was initially reported in Wuhan, Hubei Province, China, in December 2019, where patients felt SARS pneumonia-like symptoms with unknown etiology. Since then, it has been noticed that SARS-CoV-2 positive patients show mild to severe upper respiratory illness. SARS-CoV-2 belongs to the class of Coronavirus, which is known to make its transfer from animals to humans and for the concerned virus; investigators have claimed its origin from bat coronavirus at whole-genome level with a 96% sequence identity. The COVID-19 virus is extremely contagious and communicable in nature and has spread across the world since its first outbreak documented in Wuhan, China. On March 9, 2020, World Health Organization (WHO) declared it as a pandemic, and within a month, it was already reported to have shown its presence in 213 countries and territories or areas. As of Nov15, 2020, this novel virus has infected approximately. 53.7 million people and caused 1.3 million mortalities worldwide. However, the mortality rate varied between 3-13% and was influenced by a number of factors, including the demographic distribution and maybe age, comorbidities, etc. Diagnosis of the disease is a key component of controlling the spread of the virus, and several techniques, including RT-PCR, ELISA, and sequencing-based approaches, are in use. To cure COVID-19 patients, as of now, we do not have any safe and effective treatment. Currently, there is no safe and effective drug for the disease. Furthermore, various pharmaceutical industries are working on vaccine developments, which are in progress with the final stages of clinical studies. Therapeutic options are also currently under investigation in various regions of the world. However, there are various potential therapeutic targets to repurpose the present antiviral therapy for developing potential interventions against SARS-CoV-2 infection. Boosting the immune system can also help to prevent the spread of COVID-19 using various medications and exercises. Here, this review summarizes and discusses the epidemiology, evolution, transmission, and therapeutics scientific advancements related to this novel pandemic.

Background: The deadly outbreak of COVID-19 disease caused by novel SARS CoV2 has created an unprecedented global health crisis affecting every sectors of human life and enormous damage to world’s economy. With >16.1 million infections and >650,000 deaths worldwide as of July 27, 2020, there is no treatment for this disease neither is there any available vaccine. Serious research efforts are ongoing on all fronts including treatment, prevention and diagnosis to combat the spread of this infection. A number of targets that include both viral and host proteins have been identified and became part of intense investigation. In this respect the viral surface spike (S) glycoprotein caught the attention most. It is cleaved by multiple host proteases to allow recognition by host receptor human Angiotensin Converting Enzyme2 (hACE2) leading to fusion and viral replication. Natural products, small compounds, antioxidants, peptides, proteins, oligonucleotides, antibodies and other compounds are under investigation for development of antiviral agents against COVID- 19. Objective: Recently cholesterol lowering phytocompounds Quercetin, Swertiamarin and Berberine which promote human Low Density Lipoprotein Receptor (hLDLR) via inhibition of human Proprotein Convertase Subtilisin Kexin9 (hPCSK9) have been shown to block viral infections caused by ebola, influenza, Respiratory Syncytial Virus (RSV), Hepatitis C virus (HCV) and other RNA type viruses. Since SARS CoV2 is a RNA virus with similar genetic structure and infection machinery, it is hypothesised that these phytocompounds may also exhibit antiviral property against COVID-19. Methods: Our above concept is based on recently published studies as well as our herein presented in silico modeling and computational data which suggested strong interactions of hPCSK9 with above phytocompounds and most importantly with hACE2 following its complexation with receptor binding domain (RBD) of SARS CoV2 S protein. Results: These results and a proposed schematic model showing association of hPCSK9 with SARS CoV2 infection are presented in this manuscript. It is proposed that hPCSK9 plays the role of a co-receptor in binding with hACE2:RBD complex and thereby facilitates viral fusion. Conclusion: Our studies suggest that PCSK9 inhibitors may provide beneficial effect against COVID-19 infection by retarding viral fusion through displacement of bound hPCSK9 from its complex with ACE2:RBD of SARS CoV2 S protein.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is plaguing the entire world. Amidst the pandemic, research and development efforts are focused on the challenges associated with the SARS-CoV-2 structure. Materials and Methods: Efficient computational methodologies are applied to screen the available FDA-approved drugs/datasets/libraries to identify potent molecules. In the present study, we have carried out ab initio quantum chemical studies, including relativistic effects followed by molecular docking with the SARS-CoV-2 protease target by employing a tailor-made library consisting of molecular analogs of Resveratrol, a natural bioflavonoid. Results: The derived docking results were validated with ab initio quantum computations that included both density functional level (DFT) and Moller-Plesset second order perturbation theories (MP2). We found to be that Resveratrol and its analogs (R8 and R17) bind to the SARS-CoV-2 protease target. In addition to this, the computed IR spectrum is found in agreement with the reported experimental spectra for Resveratrol complexes and thus validates the modeling and reliability of proposed geometries. The solvation energies in the aqueous phase obtained using enhanced augcc- pVTZ basis sets confirm enhancement of bioavailability for Resveratrol through piperine, a natural alkaloid. Conclusion: The potential of the natural bioflavonoid Resveratrol and its analogs to be investigated through in vivo and in vitro SARS-CoV-2 protease models is concluded. The study investigated the potential of natural polyphenols as promising anti-viral therapeutics.

Background: RNA viruses evolve very fast, with a mutation rate of 103 to 105 base substitution per nucleotides per copy. The mutation is a survival strategy for the viruses, which leads them to survive in the new host. Fitness is defined as the replication capacity of the virus in an experimental setup. Generally, the large population passage of the virus leads to fitness gain, but the world data of the coronavirus infection and death shows the flattened curve with time. It is contradictory to the principle of fitness gain due to large population passage. The coronavirus is losing its potency but remains infectious as it is passaging into millions that leads to a decline in the death of COVID patients and high recovery rates. Fitness loss of coronaviruses attributed to a high level of mutation in the RNA genome as well as host immune response. The current outbreak of SARS CoV-2 is surfaced in December 2019 in Hubei province of China and considered as bats/pangolin origin, spreading 235 countries of the world, infecting nearly 31,664,104 people, and claimed nearly 972,221 lives as of September 24, 2020 (Death rate approximately 3%). This coronavirus has passaged into 31,664,104 people from the beginning of this pandemic until September 24, 2020. Now the virus is losing potency rather than being monotonous and continuous in producing virusrelated complications. The population is still getting infected at the same rate, but the severity of the disease is reduced due to the potency of the virus diminished due to the passage effect as well as fitness loss of the virus due to high mutation rates. The death rate is reduced to 3% as compared to 6% in June 2020, when this paper was first submitted. Objective: The purpose of the study is to prove the fact that the coronavirus loses its potency with time but, they remain infective. It becomes more infectious due to mutation of the gene but loses the capacity to kill the host. Methods: Since the WHO announces the COVID-19 outbreak is an emergency of international concern, every country in the world is taking many measures to mitigate the viral load to their population. Simultaneously, the WHO, CDC USA, CDC Europe, and much other organization is updating the COVID cases and death online daily as reported by the respective country. With the help of the COVID-19 outbreak data published by the European CDC and ourworldindata.org, we correlate the total cases of coronavirus and total death in the top ten affected countries in the world. We also link the trends of total cases vs. total death and total new cases vs. total new death related to COVID-19 in Germany, Spain, the United Kingdom, Italy, and New Zealand from January 30, 2020, until September 24, 2020. The reason to select these countries for the study is that these countries updating the COVID cases and deaths regularly and said to achieve the peak of COVID related infections and recovering from the pandemic. Results: We have tried to correlate the high mutation rate of the virus that leads to losing its potency to severe infection and death in the human. Viral extinction through high mutation could be considered as the new anti-viral strategies. Conclusion: Coronavirus is losing its potency to causing death to the human. The new infection is still being reported from every corner of the world, but the death rate is significantly decreasing.

As of 1st of September 2020, the COVID-19 pandemic has reached an unprecedented level of more than 25 million cases with more than 850,000 deaths. Moreover, all the drug candidates are still undergoing testing in clinical trials. In this regard, a breakthrough in drug design is necessary. One strategy to devise lead compounds is leveraging natural products as a lead source. Several companies and research institutes are currently developing anti-SARS-CoV-2 lead from natural products. Flavonoids are well known as a class of antiviral compounds library. The objective of this research is to employ virtual screening methods for obtaining the best lead compounds from the library of flavonoid compounds. This research employed virtual screening methods that comprised of downloading the protein and lead compound structures, QSAR analysis prediction, iterations of molecular docking simulation, and ADME-TOX simulation for toxicity prediction. The QSAR analysis found that the tested compounds have broad-spectrum antiviral activity, and some of them exhibit specific binding to the 3C-like Protease of the Coronavirus. Moreover, juglanin was found as the compound with the fittest binding with the Protease enzyme of SARS-CoV-2. Although most of the tested compounds are deemed toxic by the ADME-Tox test, further research should be conducted to comprehend the most feasible strategy to deliver the drug to the infected lung cells. The juglanin compound is selected as the fittest candidate as the SARS-CoV-2 lead compound in the tested flavonoid samples. However, further research should be conducted to observe the lead delivery method to the cell.