Drug Repurposing Against SARS-CoV-2

The process of repurposing drugs is an alternative to the conventional drug discovery process. It is a cost-effective and time-efficient process with high returns and low risk that utilizes mechanistic information of the existing drugs to investigate their novel applications against other disease conditions. The most significant benefit of drug repositioning is that it brings new life against novel/ orphan/ resistant diseases and pandemic outbreaks like COVID-19. As a result, widespread use of the drug repurposing strategy will not only aid in the more efficient fight against pandemics but will also combat life-threatening diseases. Therefore, repurposing drugs can provide a quick response to these unpredictable situations. In this chapter, we have tried to focus on various drug-repurposing strategies along with therapeutics for repurposing drugs against life-threatening diseases wherein little or no treatment is readily available. 

The Coronavirus Disease (COVID-19), also referred to as Novel Coronavirus Disease, is a contagious viral disease with a high rate of confirmed cases. Therefore, treatment options are urgently needed to fight the deadly virus. Since there is no standard treatment available, it results in increased morbidity and mortality. The development process of a new drug takes years, so it is crucial to focus on repurposed drugs to reduce the severity of this disease. This review aims to describe the regulatory and molecular aspects of repurposed and adjuvant drugs for COVID-19 based on registered clinical trials and online literature. The use of repurposed drugs brings its own ethical issues and challenges. The challenges of the correct interpretation of existing pre-clinical/clinical evidence and the generation of new evidence concerning drug repurposing in COVID-19 and the issues faced by the repurposing community will also be discussed in the review. When drug repurposing is employed in emergency situations, regional limitations of clinical research ethics, involuntary risk burden, regulatory aspects and ethical issues, fairness in resource distribution for repurposed drugs become an issue that requires careful ethical consideration. 

COVID-19 caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV -2), has emerged as a global health problem. It was first reported in Wuhan city of China, in December 2019. Unfortunately, no specific and effective drug is available to treat SARS-CoV-2 infection in patients. There is an urgent need to control COVID-19pandemic. Research & development of novel molecules is a timeconsuming and labour-intensive procedure in the midst of a pandemic. The aim of drug repurposing is to find a therapeutically effective molecule from a library of pre-existing compounds. In the present article, a large number of anti-viral drugs with their potential efficacy in inhibiting replication of virus by targeting the virus S protein (Spike protein), 3-chymotrypsin-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp) and papain-like protease (PLpro), which play an important role in the replication cycle and pathogenesis of coronaviruses, were assessed as possible treatment options against SARS-CoV-2 infected COVID-19 patients. The continuing SARS-CoV-2 epidemic emphasises the importance of efficient anti-viral medications that can be administered swiftly to decrease morbidity, death, and viral transmission. Several breakthroughs in the development of COVID-19 treatment options might be made by repurposing widely active anti-viral medicines and chemicals that are known to suppress viral replication of related viruses.

SARS-CoV-2 belongs to the family coronviradae and the disease caused by this virus is known as COVID-19. Viral entry into the cell is favored by spike glycoprotein, which interacts with Angiotensin-converting-enzyme-2 (ACE-2). Moreover, proteins such as Transmembrane Protease Serine-2 (TMPRSS-2), are responsible for viral fusion with cellular epithelium. Traditional drug discovery methods and their development process are time-consuming as well as expensive. Thus, there is a need for a method that can overcome such drawbacks. Drug repurposing is an approach in which we can use an existing drug that is already being used for another disease. The repurposing of drugs is also known as repositioning. It is the process that identifies new therapeutic use for existing or available drugs. Hydroxychloroquine inhibits ACE-2 glycosylation virus entry to the host body; arbidol prevents fusion of viral lipid shell with cell membrane hence restricting contact and penetration of virus. Drug repurposing could be a successful strategy for the treatment of sporadic, neglected diseases, difficult-to-treat diseases, and the current pandemic situation, i.e., COVID-19. However, there is no denying the fact that there are several limitations to this approach. 

Global public health has been challenged by the coronavirus 2019 (COVID- 19) and has been a threat to clinical management to fight this viral infection. Due to the lack of specific therapies, there is a race among the scientific fraternity to find its specific cure to date. COVID-19 symptoms range from mild fatigue to potentially fatal pneumonia, cytokine storm (CS), and multi-organ failure. Hence, investigating the repurposing of current medications for use in the management of COVID-19 patients is a realistic approach. It is prudent to investigate using repurposed medications in the management of COVID-19 patients. In the meantime, researchers are testing a number of antiviral and immunomodulatory medicines to combat the infection. Although antiviral as well as supportive medications are undoubtedly vital in the treatment of COVID-19 patients, anti-inflammatory agents play an essential part in COVID-19 patient care due to their potential to prevent additional injury and organ damage and/or failure. Moreover, COVID-19-mediated infection can be linked with coagulopathy. The most common thrombotic events in COVID-19 are venous thromboembolic (VTE), which are linked with increased severity of disease and poor clinical outcomes. Here, we evaluated medicines that potentially modulate pro-inflammatory cytokines and assist in COVID-19 management. We emphasized various pro-inflammatory cytokines as targets of repurposed drugs and targeted induction coagulation in COVID- 19 patients using the available literature and studies.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) in late 2019 has triggered an ongoing global pandemic whereby infection may result in a lethal severe pneumonia-like disease designated as coronavirus disease 2019 (COVID-19). Thus, the repositioning of known drugs can significantly accelerate the development and deployment of therapies for COVID-19.

High throughput screening (HTS) is the use of automated equipment to rapidly test thousands to millions of samples for biological activity at the model organism, cellular, pathway, or molecular level. In its most common form, HTS is an experimental process in which 103–106 small molecule compounds of known structure are screened in parallel. Currently, this technique is being used to screen known compounds in several diseases, including COVID-19. In the current scenario, it is important to focus on the application of high-throughput screening (HTS) in the drug discovery process.

In this chapter, we have covered methods of the high-throughput screen and its use in screening known drugs against infectious diseases like COVID-19. Moreover, the challenges and future of these technologies have been focussed.

In this chapter, we use computational methods to illustrate drug repurposing with the example of COVID-19. Here, the current status of drug discovery has been described with various aspects of drug repurposing interactions, use of algorithms in drug repurposing, re-evaluation of existing drugs, challenges in drug repurposing, and biological and computational interpretation of personalised and AI-guided repurposing. In addition, we present blueprints for pacing up the drug repurposing process using artificial intelligence. This chapter is devoted to the use of computational intelligence for drug repurposing against various diseases, including COVID-19.