COVID-19: A state of art on immunological responses, mutations, and treatment modalities in riposte.

Over the last few years, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) unleashed a global public health catastrophe that had a substantial influence on human physical and mental health, the global economy, and socio-political dynamics. SARS-CoV-2 is a respiratory pathogen and the cause of ongoing COVID-19 pandemic, which testified how unprepared humans are for pandemics. Scientists and policymakers continue to face challenges in developing ideal therapeutic agents and vaccines, while at the same time deciphering the pathology and immunology of SARS-CoV-2. Challenges in the early part of the pandemic included the rapid development of diagnostic assays, vaccines, and therapeutic agents. The ongoing transmission of COVID-19 is coupled with the emergence of viral variants that differ in their transmission efficiency, virulence, and vaccine susceptibility, thus complicating the spread of the pandemic. Our understanding of how the human immune system responds to these viruses as well as the patient groups (such as the elderly and immunocompromised individuals) who are often more susceptible to serious illness have both been aided by this epidemic. COVID-19 causes different symptoms to occur at different stages of infection, making it difficult to determine distinct treatment regimens employed for the various clinical phases of the disease. Unsurprisingly, determining the efficacy of currently available medications and developing novel therapeutic strategies have been a process of trial and error. The global scientific community collaborated to research and develop vaccines at a neck-breaking speed. This review summarises the overall picture of the COVID-19 pandemic, different mutations in SARS-CoV-2, immune response, and the treatment modalities against SARS-CoV-2.

Thermostable vaccines: an innovative concept in vaccine development.

INTRODUCTION: Vaccines represent he most common and safer ways of combating infectious diseases. Loss of potency owing to thermal denaturation or degradation of almost all the vaccines necessitates their storage, transportation, and final dissemination under refrigerated conditions. However, maintenance of a continuous cold chain raises the costs of vaccines significantly. A large number of life-saving vaccines are discarded before their application owing to exposure to sub-optimum temperatures. Therefore, there is a pressing need for the development of a thermostable vaccine with a long shelf life at ambient temperature. AREAS COVERED: A literature search was performed to compile a list of different vaccines, and their storage and handling conditions. Similarly, a separate list was prepared for different coronavirus vaccines. A literature survey was also performed to look at different approaches undertaken globally to address the issue of the cold-chain problem. We emphasized the importance of yeast cells in the development of thermostable vaccines. In the end, we discussed why thermostable vaccines are required, not only in resource-poor countries but also for resource-rich countries . EXPERT OPINION: Temperature change can severely impact the stability of various life-saving vaccines. Therefore, there is a pressing need for the development of thermostable vaccines with a long shelf lives.

Mucormycosis and COVID-19 pandemic: Clinical and diagnostic approach.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is yet to be controlled worldwide, especially in India. The second wave of coronavirus disease 2019 (COVID-19) led to panic and confusion in India, owing to the overwhelming number of the population that fell prey to this highly infectious virus of recent times. In the second wave of COVID-19, the patients had to fight both the virus and opportunistic infections triggered by fungi and bacteria. Repeated use of steroids, antibiotics, and oxygen masks during the management of severely and critically ill COVID-19 patients nurtured opportunistic infections such as mucormycosis. Despite mucormycosis being a decades-old disease, it has gained notice of its widespread occurrence in COVID-19 patients throughout India. Instances of mucormycosis are usually unearthed in immunocompromised individuals and are caused by the inhalation of filamentous fungi, either from the natural environment or through supportive care units. In the recent outbreak during the second wave of COVID-19 in India, it has been seen to cause secondary infection as it grows along with the treatment of COVID-19. Furthermore, COVID-19 patients with comorbidities such as diabetes were more likely to have the mucormycosis co-infection because of their challenged immune systems' inability to fight it. Despite the hype, mucormycosis still remains neglected and least studied, which is predominantly due to all focus on diagnostics, vaccine, and therapeutic research. In this review, we emphasize mainly on the association of mucormycosis in COVID-19 patients. We also present the molecular mechanism of mucormycosis for a better understanding of the fungal infections in patients who have recently been infected with SARS-CoV-2. Better understanding of fungal pathogens, immediate diagnosis, and management of the infections are crucial in COVID-19 patients, as high mortalities have been recorded in co-infected patients despite recovery from COVID-19.

New perspective towards therapeutic regimen against SARS-CoV-2 infection.

The ongoing enormous loss of human life owing to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has led to a global crisis ranging from the collapse of health - care systems to socio-economic instability. As SARS-CoV-2 is a novel virus, very little information is available from researchers and therefore, a rigorous effort is required to decode its pathogenicity. There are no licenced treatment options available for treating SARS-CoV-2 infections and the development of a new antiviral drug targeting coronavirus cannot happen soon. Consequently, drug repurposing is a promising solution for combating the present pandemic. In this review, we have thoroughly discussed all the proteins encoded by the SARS-CoV-2 genome; their importance in pathogenicity and their potential role in drug discovery. Also, the budding threat of co-infections by other pathogenic microbes has been highlighted. Furthermore, the advances made in the medicinal field for the treatment and prevention of this viral infection is explained. Altogether, this review will provide some insightful discussions about this infectious disease and will meet certain of the knowledge gaps which exist by presenting an exhaustive and extensive scientific report on the ongoing mission for COVID-19 drug discovery.

ABBV-744 as a potential inhibitor of SARS-CoV-2 main protease enzyme against COVID-19.

A new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and become pandemic with thousands new deaths and infected cases globally. To address coronavirus disease (COVID-19), currently no effective drug or vaccine is available. This necessity motivated us to explore potential lead compounds by considering drug repurposing approach targeting main protease (Mpro) enzyme of SARS-CoV-2. This enzyme considered to be an attractive drug target as it contributes significantly in mediating viral replication and transcription. Herein, comprehensive computational investigations were performed to identify potential inhibitors of SARS-CoV-2 Mpro enzyme. The structure-based pharmacophore modeling was developed based on the co-crystallized structure of the enzyme with its biological active inhibitor. The generated hypotheses were applied for virtual screening based PhaseScore. Docking based virtual screening workflow was used to generate hit compounds using HTVS, SP and XP based Glide GScore. The pharmacological and physicochemical properties of the selected lead compounds were characterized using ADMET. Molecular dynamics simulations were performed to explore the binding affinities of the considered lead compounds. Binding energies revealed that compound ABBV-744 binds to the Mpro with strong affinity (ΔGbind -45.43 kcal/mol), and the complex is more stable in comparison with other protein-ligand complexes. Our study classified three best compounds which could be considered as promising inhibitors against main protease SARS-CoV-2 virus.

Structure-based identification of potential SARS-CoV-2 main protease inhibitors.

To address coronavirus disease (COVID-19), currently, no effective drug or vaccine is available. In this regard, molecular modeling approaches are highly useful to discover potential inhibitors of the main protease (Mpro) enzyme of SARS-CoV-2. Since, the Mpro enzyme plays key roles in mediating viral replication and transcription; therefore, it is considered as an attractive drug target to control SARS-CoV-2 infection. By using structure-based drug design, pharmacophore modeling, and virtual high throughput drug screening combined with docking and all-atom molecular dynamics simulation approach, we have identified five potential inhibitors of SARS-CoV-2 Mpro. MD simulation studies revealed that compound 54035018 binds to the Mpro with high affinity (ΔGbind -37.40 kcal/mol), and the complex is more stable in comparison with other protein-ligand complexes. We have identified promising leads to fight COVID-19 infection as these compounds fulfill all drug-likeness properties. However, experimental and clinical validations are required for COVID-19 therapy.Communicated by Ramaswamy H. Sarma.

COVID-19 pandemic - an African perspective.

The recently emerged novel coronavirus, "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)", caused a highly contagious disease called coronavirus disease 2019 (COVID-19). The virus was first reported from Wuhan city in China in December, 2019, which in less than three months spread throughout the globe and was declared a global pandemic by the World Health Organization (WHO) on 11th of March, 2020. So far, the ongoing pandemic severely damaged the world's most developed countries and is becoming a major threat for low- and middle-income countries. The poorest continent, Africa with the most vulnerable populations to infectious diseases, is predicted to be significantly affected by the ongoing COVID-19 outbreak. Therefore, in this review we collected and summarized the currently available literature on the epidemiology, etiology, vulnerability, preparedness and economic impact of COVID-19 in Africa, which could be useful and provide necessary information on ongoing COVID-19 pandemics in the continent. We also briefly summarized the concomitance of the COVID-19 pandemic and global warming.