A systematic review on SARS-CoV-2 remission: an emerging challenge for its management, treatment, immunization strategies, and post-treatment guidelines.

The COVID-19 disease caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2) has posed as a major health concern for people all across the globe. Along with the increasing confirmed patients being readmitted with complaints for fever, cough, cold, the effective monitoring of 'relapse' of the SARS-CoV-2 virus in the previously discharged patients have become the next area of focus. However, availability of limited data on reactivation of SARS-CoV-2 makes the disease prognosis as well as the effective control of re-infection an immense challenge. Prompted by these challenges, we assessed the possibility of re-infection in discharged patients and the risk of the transmission, proficiency of RT-PCR results and approximate period required for the quarantine, and the real challenges for the development of vaccine. In the present review, the published literature on all the possible cases of re-infection from February to July were reported, thereby selected 142 studies from a hub of overall 669 studies after full text screening. The incomplete virus clearance, poor sensitivity of the present diagnostic testing, emergence of mutant strains, insufficient mucus collection from the throat swab etc., are some of the possible causes of re-infection. The new protocols for management of COVID-19 discharged patients should be revised in the guidelines.

Computational Modeling of ACE2 Inhibitors for Development of Drugs Against Coronaviruses

Despite the declaration of SARS-CoV-2 infection as a pandemic on March 11, 2020 by the World Health Organization, till date, no effective treatment has been approved to combat the severity of this pandemic. Few antiviral and antimalarial drugs have been used for symptomatic treatment of COVID-19 infection, but none of the treatment strategies has provided promising results against this infection. As the journey of a vaccine is also very long, there is a need to repurpose the already approved drugs against this pandemic. The urge of studying the structural association of human ACE2, an entry receptor of the virus in the human body with the SARS-CoV-2, may lead to the invention of a new promising prophylactic as well as curative treatment options for the COVID-19 pandemic. This chapter covers the importance of human ACE2 receptors in pathophysiology of COVID-19 infection. Finally, the results of various computational studies have been elaborated in this chapter. The role of different classes of already approved drugs which have shown promise against SARS-CoV-2 infection in in silico docking and computational modeling experiments is summarized for their future prospects in the treatment of COVID-19 infection. They were chosen on the basis of their free binding energies and relative ligand scoring scales. Molecular docking tools like molecule operating environment (MOE), Glide, AutoDock Vina, and Swiss dock were used in many in silico experiments. Some of the potential treatment modalities found in literature survey were ACE inhibitors, antibiotics, anti-inflammatory, antineoplastic, phosphodiesterase inhibitors, hydroxychloroquine and chloroquine, and so on, which have been proved to be efficacious treatment options for SARS-CoV-2 infection by computational modeling of human ACE2 receptors.

Machine Learning Techniques for Development of Drugs Against Coronavirus Disease 2019 (COVID-19): A Case Study Protocol

Discovery of SARS-CoV-2 drug requires a fast track approach to achieve the effective and safe alternative. The present times call for an evolution in the process of drug discovery. Several factors contribute to high cost and long development times associated with new drugs. Finding a new molecular target is contingent upon a detailed understanding of the disease pathology, which often takes years of basic research. Integrating genetic and expression studies with Protein Interaction Network (PIN), and considering both functional and topological features of the resultant network may prove to be an effective target identification strategy. Further, apart from the existing computational tools to identify ligands, artificial intelligence approaches may now be used to increase the search space many folds, offering a faster method for screening. Artificial intelligence can be integrated with the existing drug discovery pipeline to enable rational target identification, prediction of an accurate 3D structure of the molecular target and screen large ligand libraries for putative modulators. The present chapter covers a detailed protocol to scan and validate the therapeutic targets for COVID-19, and screen the compounds for future in vitro or in vivo validation. The chapter covers target selection strategies, and application of artificial intelligence to identify drug–target interactions.

Hydroxychloroquine drug safety review for the prophylaxis of SARS COV 2 pandemic

COVID19 outbreak, originated from Wuhan, China is now declared as pandemic by WHO. HCQ has got special attention after various advisories are being issued by health authorities to utilize it for the prophylaxis of SARS COV2. Therefore, drug safety evaluation based on its pharmacokinetic & pharmacodynamics parameters & literature rationale for Evidence Based Medicine is required for its justification to be utilize effectively in the COVID19 Pandemic. We have reviewed literature of HCQ antiviral properties, ADRs, Drug Interactions on PubMed, Google Scholar, CDC database etc. Based on the gathered evidences we have performed Evidence Based Medicine (EBM) Risk vs. Benefit Analysis to justify HCQ utilization in SARS COV 2 through U.S. Preventive Services Task Force guidelines. Adverse drug reactions & toxicities such as retinopathy & cardiotoxicity due to HCQ are dose dependent and preventable in nature. HCQ has a potency to combat the disease. Further confirmations are awaited by more clinical trials and their meta-analysis results. It has proven to be effective in inhibiting the viral entry into the cell membrane & decreasing the viral duration of SARS COV 2 in cell culture as well in RCT. In this hour of great disaster where no other safe option appears to be much effective, we conclude that HCQ prophylactic and therapeutic benefits against COVID19 epidemic outweighs the potential risks of adverse drug reactions, which are preventable in nature. For desired therapeutic response, careful monitoring is advised.

BCG as a game-changer to prevent the infection and severity of COVID-19 pandemic?

The impact of COVID-19 is changing with country wise and depend on universal immunization policies. COVID-19 badly affects countries that did not have universal immunization policies or having them only for the selective population of countries (highly prominent population) like Italy, USA, UK, Netherland, etc. Universal immunization of BCG can provide great protection against the COVID-19 infection because the BCG vaccine gives broad protection against respiratory infections. BCG vaccine induces expressions of the gene that are involved in the antiviral innate immune response against viral infections with long-term maintenance of BCG vaccine-induced cellular immunity. COVID-19 cases are reported very much less in the countries with universal BCG vaccination policies such as India, Afghanistan, Nepal, Bhutan, Bangladesh, Israel, Japan, etc. as compared to without BCG implemented countries such as the USA, Italy, Spain, Canada, UK, etc. BCG vaccine provides protection for 50-60 years of immunization, so the elderly population needs to be revaccinated with BCG. Several countries started clinical trials of the BCG vaccine for health care workers and elderly people. BCG can be uses as a prophylactic treatment until the availability of the COVID-19 vaccine.