Coronaviruses - Volume 3, Issue 4, 2022

Coronaviruses are a leading cause of emerging life-threatening diseases, as evidenced by the ongoing coronavirus disease pandemic (COVID-19). According to complete genome sequence analysis reports, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, has a sequence identity highly similar to the earlier severe acute respiratory syndrome coronavirus (SARSCoV). The SARS-CoV-2 has the same mode of transmission, replication, and pathogenicity as SARSCoV. The SARS-CoV-2 spike protein's receptor-binding domain (RBD) binds to host angiotensinconverting enzyme-2 (ACE2). The ACE2 is overexpressed in various cells, most prominently epithelial cells of the lung (surface of type 1 and 2 pneumocytes), intestine, liver, kidney, and nervous system. As a result, these organs are more vulnerable to SARS-CoV-2 infection. Furthermore, renin-angiotensin system (RAS) blockers, which are used to treat cardiovascular diseases, intensify ACE2 expression, leading to an increase in the risk of COVID-19. ACE2 hydrolyzes angiotensin- II (carboxypeptidase) to heptapeptide angiotensin (1-7) and releases a C-terminal amino acid. By blocking the interaction of spike protein with ACE2, the SARS-CoV-2 entry into the host cell and internalization can be avoided. The pathogenicity of SARS-CoV-2 could be reduced by preventing the RBD from attaching to ACE2-expressing cells. Therefore, inhibition or down-regulation of ACE2 in host cells represents a therapeutic strategy to fight against COVID-19. However, ACE2 plays an essential role in the physiological pathway, protecting against hypertension, heart failure, myocardial infarction, acute respiratory lung disease, and diabetes. Given the importance of ACE's homeostatic role, targeting of ACE2 should be realized with caution. Above all, focusing on the SARS-CoV-2 spike protein and the ACE2 gene in the host cell is an excellent way to avoid viral mutation and resistance. The current review summarises the sequence analysis, structure of coronavirus, ACE2, spike protein-ACE2 complex, essential structural characteristics of the spike protein RBD, and ACE2 targeted approaches for anti-coronaviral drug design and development.

A more focused approach is needed to understand the SARS-CoV-2 virulence, structure, and genomics to devise more effective diagnostic and treatment interventions as this virus can evade the immune attack and causes life-threatening complications such as cytokine storm. The spread of the virus is still amplifying and causing thousands of new cases worldwide. It is essential to review current diagnostics and treatment approaches to pave the way to correct or modify our current practices to make more effective interventions against COVID-19. COVID-19 vaccine development has moved at a breakneck pace since the outbreak began, utilizing practically all possible platforms or tactics to ensure the success of vaccines. A total of 42 vaccine candidates have already entered clinical trials, including promising results from numerous vaccine candidates in phase 1 or phase 2 trials. Further, many existing drugs are being explored on broad-spectrum antiviral medications for their use in clinical recovery against COVID- 19. The present review attempts to re-examine the SARS-CoV-2 structure, its viral life cycle, clinical symptoms and pathogenesis, mode of transmission, diagnostics, and treatment strategies that may be useful for resorting to more effective approaches for controlling COVID-19. Various antiviral drugs and vaccination strategies with their strengths and weaknesses are also discussed in the paper to augment our understanding of COVID-19 management.

The strategy of drug repurposing has been proved successful in response to the current coronavirus pandemic, with remdesivir becoming the first drug of choice, an antiviral drug approved for the treatment of COVID-19. In parallel to this, several drugs, such as antimalarial, corticosteroids, and antibiotics, like azithromycin, are used to treat the severe condition of hospitalized COVID-19 patients, while clinical testing of additional therapeutic drugs, including vaccines, is going on. It is reasonably expected that this review article will deliver optimized and specific curative tools that will increase the attentiveness of health systems to the probable outlook of epidemics in the future. This review focuses on the application of repurposed drugs by studying their structure, pharmacokinetic study, different mechanisms of action, and Covid-19 guidelines, which can potentially influence SARS-CoV-2. For most of the drugs, direct clinical evidence regarding their effectiveness in the treatment of COVID-19 is missing. Future clinical trial studies may conclude that one of these can be more potential to inhibit the progression of COVID-19.

The novel coronavirus infection (COVID-19) is a global public health emergency. Since its outbreak in Wuhan, China in December 2019, the infection has spread at an alarming rate across the globe and humans have been locked down to their countries, cities and homes. As of now, the virus has affected over 20 million people globally and has inflicted over 7 lac deaths. Nevertheless, the recovery rate is improving with each passing day and over 14 million people have recuperated so far. The statistics indicate that nobody is immune to the disease as the virus continues to spread among all age groups, newborns to the elders, and all compartments including pregnant women. However, pregnant women may be more susceptible to this infection as they are, in general, highly vulnerable to respiratory infections. There is no evidence for vertical transmission of the COVID-19 virus among pregnant women, but an increased prevalence of preterm deliveries. Besides this, the COVID-19 may alter immune response at the maternal-fetal interface and affect the well-being of mothers as well as infants. Unfortunately, there is limited evidence available in the open literature regarding coronavirus infection during pregnancy and it now appears that certain pregnant women have been infected during the present 2019-nCoV pandemic. In this perspective, we study the impact of the COVID-19 infection on vertical transmission and fetal outcomes among pregnant women.

Background: The strange and still unclear scenarios of COVID-19 pandemic development have raised the question about the reason for the observed essential state and personal differences concerning the expansion and severity of the infection process. Some custom activities are taken into consideration in an attempt to explain the phenomenon. Alcohol in the diet is suggested in this paper as the possible factor which could explain the observed differentiation. It easily penetrates cells modifying their natural internal environment, and independently influences tissues as the toxic agent being the source of acetyl aldehyde. Objective: The process in which the cell seems to be the most sensitive to altered environmental conditions is the protein folding; in particular, its portion occurring in the endoplasmic reticulum where freshly synthesized polypeptides fold and then are introduced to the cell membrane influencing its property and in particular its fluidity, which is the critical parameter deciding the virus penetration into the cell. Methods: The application of a mathematical model, fuzzy oil drop model FOD, expressing the influence of the environment on the protein folding process shows the mechanism of this influence. Results: The differences between statistical assessment of epidemy in Europe and the Far East, which may be correlated with alcohol consumption, suggest the influence of diet on the status of epidemy in these regions. Conclusion: The protein folding seems to be the process most sensitive to environmental conditions in the cell. The different diet customs, including the use of alcohol, may disturb the folding process, lowering as the result the number of proteins needed for cell membrane stability, thus increasing its fluidity and the cell susceptibility to virus penetration. Observations presented in this paper are based on the initial period of pandemic development and have not been intentionally modified to prevent the influence of additional factors, like government activities or virus mutations.

Background: Coronavirus Disease 2019 (COVID-19), one of the greatest challenges facing humanity, continues to affect millions of people worldwide. Vaccines approved and authorized for use are effective against COVID-19, but viral variants of concern may emerge in the near future. The discovery of novel antiviral agents will help humanity overcome COVID-19 and aid in any future viral pandemics. Objective: This review aimed to evaluate evidence from the plant- and seaweed-derived secondary compound- based interventions for viral diseases caused by coronaviruses. Methods: A comprehensive search of several databases, including Cochrane Library, Web of Science and PubMed was conducted to identify available studies evaluating the outcomes of plant- and seaweed secondary metabolites in viral diseases such as Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome and COVID-19. Results: The volume of existing reports is irrefutable evidence that some plant- and seaweed-derived secondary compounds (e.g., mannose-specific lectins, griffithsin, cyanovirin-N, gallate, curcumin, luteolin, quercetin and betulinic acid) possess a potential antiviral ability against coronaviruses, including SARS-CoV-2. Conclusion: Plant and seaweed secondary metabolites with antiviral activity show their activity in different metabolic pathways. Besides reducing and preventing the metabolic damage caused by proinflammatory cytokines and oxidative stress, several plants and seaweed secondary metabolites can also be effective in improving some clinical indexes specific to COVID-19. Despite their effectiveness in preclinical studies, plant and seaweed-derived secondary compounds need more pharmacokinetic studies and safety measures concerning their mitogenic and allergenic properties.

Background: Coronavirus disease (COVID 19) has been emerging as a major threat to humans all over the world. Severe Acute Respiratory Syndrome CoronaVirus 2 (nSARS-CoV-2) is the causative agent for the disease resulting in severe acute respiratory illness. Earlier, it took several years to come up with a vaccine or other sorts of treatments for viral diseases. But now with the advent of biotechnology and development of bio-informatic tools, the process has been accelerated. The WHO reports 39,806,488 affected cases and 1,112,208 deaths till today all over the world (17 Oct 2020). nSARS-CoV-2 has a greater influence on people with comorbidities mainly cancer. Objective: The study herein attempts to understand the binding affinity of the spike protein of the novel coronavirus with the lung and breast cancer marker proteins by docking and ClusPro analysis. Methods: The analysis was conducted in reference to hACE2 (human Angiotensin Converting Enzyme 2), the receptor of nSARS-CoV-2. Total 22 different marker proteins were analyzed using ClusPro. Results: BRCA1 (Breast Cancer type 1 susceptibility protein) and CXCR4 (a chemokine receptor belonging to the G protein coupled receptor family) were found to exhibit higher binding affinities.-73.82 kcal/mol and -66.45 kcal/mol were the global energies they showed upon binding to S protein respectively. Conclusion: Therefore, novel SARS-CoV-2 has a higher chance of inducing cancer in non-cancerous individuals and aids in cancer acceleration in cancer patients . This poses a threat to cancer patients and immunocompromised individuals. The study can be exploited to identify the optimal drug delivery system for novel SARS CoV2.