Coronavirus belongs to the family of Coronaviridae, comprising single-stranded, positive-sense RNA genome (+ ssRNA) of around 26 to 32 kilobases, and has been known to cause infection to a myriad of mammalian hosts, such as humans, cats, bats, civets, dogs, and camels with varied consequences in terms of death and debilitation. Strikingly, novel coronavirus (2019-nCoV), later renamed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and found to be the causative agent of coronavirus disease-19 (COVID-19), shows 88% of sequence identity with bat-SL-CoVZC45 and bat-SL-CoVZXC21, 79% with SARS-CoV and 50% with MERS-CoV, respectively. Despite key amino acid residual variability, there is an incredible structural similarity between the receptor binding domain (RBD) of spike protein (S) of SARS-CoV-2 and SARS-CoV. During infection, spike protein of SARS-CoV-2 compared to SARS-CoV displays 10–20 times greater affinity for its cognate host cell receptor, angiotensin-converting enzyme 2 (ACE2), leading proteolytic cleavage of S protein by transmembrane protease serine 2 (TMPRSS2). Following cellular entry, the ORF-1a and ORF-1ab, located downstream to 5′ end of + ssRNA genome, undergo translation, thereby forming two large polyproteins, pp1a and pp1ab. These polyproteins, following protease-induced cleavage and molecular assembly, form functional viral RNA polymerase, also referred to as replicase. Thereafter, uninterrupted orchestrated replication-transcription molecular events lead to the synthesis of multiple nested sets of subgenomic mRNAs (sgRNAs), which are finally translated to several structural and accessory proteins participating in structure formation and various molecular functions of virus, respectively. These multiple structural proteins assemble and encapsulate genomic RNA (gRNA), resulting in numerous viral progenies, which eventually exit the host cell, and spread infection to rest of the body. In this review, we primarily focus on genomic organization, structural and non-structural protein components, and potential prospective molecular targets for development of therapeutic drugs, convalescent plasm therapy, and a myriad of potential vaccines to tackle SARS-CoV-2 infection.

Zika virus (ZIKV), belongs to the flavivirus genus and Flaviviridae family that associated with serious diseased conditions like microcephaly and other neurological disorders (Guillan–Barré syndrome). As there is no vaccine or therapies available against ZIKV to date. Hence, it is an unmet need to find potential drug candidates and target sites against Zika virus infection. NS2B-NS3 protease making an attractive target for therapeutic intervention in ZIKV infections because of its critical role in hydrolysis of a single polyprotein encoded by Zika virus. Recently, there are some experimental evidence about the flavonoids as Zika virus NS2B-NS3 protease inhibitors. However, molecular interaction between protease complex and inhibitors at atomic levels has not been explored. Here, we have taken the experimentally validated thirty-eight flavonoids inhibitors against NS2B-NS3 protease to examine the molecular interaction using molecular docking and molecular dynamics simulations. We found out few flavonoids such as EGCG and its two derivatives, isoquercetin, rutin and sanggenon O showing interaction with catalytic triad (His51, Asp75, and Ser135) of the active site of NS2B-NS3 protease and found to be stable throughout the simulation. Therefore it is evident that interaction with the catalytic triad playing a vital role in the inhibition of the enzyme activity as a result inhibition of the virus propagation. However these compounds can be explored further for understanding the mechanism of action of these compounds targeting NS2B-NS3 protease for inhibition of Zika virus. Investigating into the Molecular Interactions of Flavonoids targeting NS2B-NS3 protease from ZIKA virus through in-silico approaches ZIKA virus protease (NS2B-NS3pro) is essential for ZIKA virus replication and maturation. Therefore targeting this protein complex with potential inhibitors will block the viral replication. Here we revealed the interaction of the flavonoids, a successful ZIKA NS2B-NS3pro inhibitors through Molecular modeling and Simulation studies. Communicated by Ramaswamy H. Sarma

The first quarter of the 21st century has remarkably been characterized by a multitude of challenges confronting human society as a whole in terms of several outbreaks of infectious viral diseases, such as the 2003 severe acute respiratory syndrome (SARS), China; the 2009 influenza H1N1, Mexico; the 2012 Middle East respiratory syndrome (MERS), Saudi Arabia; and the ongoing coronavirus disease 19 (COVID-19), China. COVID-19, caused by SARS-CoV-2, reportedly broke out in December 2019, Wuhan, the capital of China’s Hubei province, and continues unabated, leading to considerable devastation and death worldwide. The most common target organ of SARS-CoV-2 is the lungs, especially the bronchial and alveolar epithelial cells, culminating in acute respiratory distress syndrome (ARDS) in severe patients. Nevertheless, other tissues and organs are also known to be critically affected following infection, thereby complicating the overall aetiology and prognosis. Excluding H1N1, the SARS-CoV (also referred as SARS-CoV-1), MERS, and SARS-CoV-2 are collectively referred to as coronaviruses, and taxonomically placed under the realm Riboviria, order Nidovirales, suborder Cornidovirineae, family Coronaviridae, subfamily Orthocoronavirinae, genus Betacoronavirus, and subgenus Sarbecovirus. As of 23 September 2021, the ongoing SARS-CoV-2 pandemic has globally resulted in around 229 million and 4.7 million reported infections and deaths, respectively, apart from causing huge psychosomatic debilitation, academic loss, and deep economic recession. Such an unprecedented pandemic has compelled researchers, especially epidemiologists and immunologists, to search for SARS-CoV-2-associated potential immunogenic molecules to develop a vaccine as an immediate prophylactic measure. Amongst multiple structural and non-structural proteins, the homotrimeric spike (S) glycoprotein has been empirically found as the most suitable candidate for vaccine development owing to its immense immunogenic potential, which makes it capable of eliciting both humoral and cell-mediated immune responses. As a consequence, it has become possible to design appropriate, safe, and effective vaccines, apart from related therapeutic agents, to reduce both morbidity and mortality. As of 23 September 2021, four vaccines, namely, Comirnaty, COVID-19 vaccine Janssen, Spikevax, and Vaxzevria, have received the European Medicines Agency’s (EMA) approval, and around thirty are under the phase three clinical trial with emergency authorization by the vaccine-developing country-specific National Regulatory Authority (NRA). In addition, 100–150 vaccines are under various phases of pre-clinical and clinical trials. The mainstay of global vaccination is to introduce herd immunity, which would protect the majority of the population, including immunocompromised individuals, from infection and disease. Here, we primarily discuss category-wise vaccine development, their respective advantages and disadvantages, associated efficiency and potential safety aspects, antigenicity of SARS-CoV-2 structural proteins and immune responses to them along with the emergence of SARS-CoV-2 VOC, and the urgent need of achieving herd immunity to contain the pandemic.

Acute kidney injury (AKI) following cardiac surgery is a common complication associated with serious morbidity and mortality. Activation of inflammatory cascade and vascular endothelial dysfunction plays a vital role during the perioperative period leading to AKI. Statins are known to suppress inflammation and improve endothelial dysfunction over and above the cholesterol lowering efficacy. Observational studies with a defined population in terms of preoperative statin therapy and no preoperative statin therapy undergoing cardiac surgery (CABG, isolated valve surgery or both) and with reported data on the incidence of acute renal failure/injury and/or mortality were identified and analysed for inclusion in the analysis. Outcomes evaluated were occurrence of postoperative acute kidney injury/failure, requirement of any postoperative renal replacement therapy and short-term all-cause mortality rate. A meta-analysis was conducted and a pooled estimate of odds ratio (OR) was calculated using the inverse variance method. A total of 17 studies with a total population of 24 998 statin users and 22 082 non-statin users were included in the final analysis. PST resulted in a significantly lower incidence of renal replacement therapy in patients undergoing CABG (OR: 0.56 [0.41–0.76]) but not in isolated valve surgery (OR: 1.80 [0.73–4.44]). Also preoperative statin therapy resulted in a significantly lower postoperative mortality (0.72 [0.61–0.84]) irrespective of the type of surgery. There was no effect of preoperative statin therapy on the incidence of AKI in any of the sub-group of the patients. Patients undergoing CABG might derive benefit from preoperative statin therapy in terms of reducing the need for postoperative renal replacement therapy and mortality. However, the uncertainty concerning the reno-protective efficacy of preoperative statin therapy in patients undergoing isolated valve surgery needs further investigation.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Drug related events include ADRs, events due to patient or physician noncompliance, drug overdosage and drug interactions.• Economic burden of management of drug related events are substantial and include both direct and indirect costs.• Some data regarding cost of treatment of ADR exist from south and western India. WHAT THIS STUDY ADDS • An approximate cost of management of drug related events presenting to the emergency medical department in a tertiary care hospital over a period of 4 months.• Compares the cost incurred in a public sector hospital to the projected cost of management of same events in a private sector hospital.• Gives a rough estimate of economic burden on the health care system due to adverse drug events.AIMS Drug related events (DREs) contribute significantly to hospital admissions. These are largely preventable events and require optimum use of the therapeutic agents. The study was conducted to analyze the cost of treatment of DREs.PATIENTS & METHODS All visits to medical emergency department of a tertiary care public sector hospital in northern India were recorded in a prospective, non‐interventional manner over a period of 4 months. DREs were recognized and were followed up till their stay in the hospital. Data about the cost generating components of direct and indirect costs of treatment of DREs were collected. The projected cost of treatment of the same DREs in a private sector hospital was estimated and compared.RESULTS Out of 1833 admissions, 92(5.01%) were due to DREs. Maximum cases were due to non compliance (66%) followed by ADR (28%) and drug overdose(6%). The common DREs leading to ED visits were cerebrovascular accident(19.44%), followed by accelerated hypertension(18.36%) and diabetic ketoacidosis(14.04%). Total cost of management of all the 92 DREs in our hospital was calculated to be INR17,37,339(€30,215). The direct cost was INR1,72,961(€3008) and the approximate indirect cost was INR15,64, 378(€27, 206). The projected cost of management of all the 92 DREs was estimated to be INR63,63,872(€1,01, 676) in a private sector hospital.CONCLUSION The study shows that ADEs leading to emergency department visits and hospitalizations constitute a significant economic burden. Training of the patients and the prescribers may lessen the economic burden on the patient as well as the health care system.