**1. Introduction**

Drug Repurposing, repositioning and reprofiling is trending initiative adopted by the researcher to identify the new target with existing drug molecule, the chemotherapeutic intervention of antiviral drugs discovery, frequently unsynchronized with development and licensing of the new drug, diseased caused by the virous is not an exceptional way of treating with antiviral agents. COVID-19 was turnout to be the major pandemic of the 21st century which is highly contagious, with more the 200 million cases and 4.5 million deaths worldwide to date, this pandemic created

wreaked havoc in society with immense human suffering. In a race against time to stop the spread of the disease. Contemporaneous endeavor scientific research community put forth several active molecules which inhibit the SARS-CoV-2 infection within period. Based on the background of literature report viral entry and replication within the host of the cell involves multiple molecular factors associated with the host and virous both, among this important one is a Main protease (Mpro), which is also referred to as 3C-like protease (3C-Lpro). Mpro cleavage of the viral polyprotein PP1ab at 11 discrete sites (polyproteins encoded with Leu-Gly-fl-Ser/Gly/Ala as motif cleavage). After cleavage it released non-structural protein from replicase complex, which is essential for viral replication, the proteolytic cleavage inhibition can prevent SARS-CoV-2 replication inside the host cell, hence in antiviral drug discovery, the Mpro is a prime target against SARS-CoV-2. Beginning of the first case of COVID-19, intensive literature reviled that Mpro is prime suspect targeted with several drug candidates which include both ab initio designed as well as repositioning of drugs. Notable recent discovery reports on repositioning approach with electrophilic and noncovalent fragment screening against Mpro in combination with Mass spectrometry and X-ray crystallography found to be an excellent technique to figure out the active site as well as dimerization interface, several potent small-molecule inhibitors of SARS-CoV-2 Mpro were predicted in a recent year since the beginning of this pandemic outbreak with all-inclusive nature of work vindicated by the discovery of both mentioned above in the paragraph.

However, to be noted here, 12 antiviral drugs were approved by FDA in the USA till date, among these 8 are used to treat hepatitis C virus (HCV)-related pathologies and 2 are in the combination of anti-human immunodeficiency virus (HIV) agents. WHO


**Table 1.**

*Precedence and pitfalls of a drug repurposing approach for antiviral drug discovery.*

*Reprofiling of Octogenarian Antiviral Agent: A New Avenue Venture to Discover Viral Infection DOI: http://dx.doi.org/10.5772/intechopen.102825*


**Table 2.**

*Small-molecule libraries used in antiviral drug repurposing.*

dealing with the re-emerging viruses responsible for pandemic potential and alarming outbreak in recent years, which was still lacking specific treatment, such as Zika virus (ZIKV), Ebola Virus (EBOV), Middle East respiratory syndrome coronavirus (MERS-CoV), COVID-19, delta virus and nowadays the popular one OMICRON. The recent advancement in controlling this viral pathogen, drug discovery in the drug repurposing approach emerged as giving the old drug to new symptoms which unlock the unidentified molecular pathway with the target of intervention. Basically, this strategy was adopted to combat viral infectious disease, by integrating with combination with computational methods (in silico screening, mining of database with transcriptomic profile, etc. (**Tables 1** and **2**), and collective screening of small bioactive molecules.

**Figure 1.** *DD and DR pathway.*

Unquestionably a new drug development, in order to search for the lead molecule or pathway with biological screening that could be recycled against the viral pathogen, will be a competitive economic advantage, on the level of fundamental needs, indeed repurposed drugs quickly enter the clinical trial especially in case of viral disease lacking specified treatment (**Figure 1**) [1].

DR represents the constant source, to update and upgrade, cognition, in viral biology with available antiviral molecules hidden potentiality, which comes out as a tool to unlock the molecular mechanisms of virous replication and pathogenesis. No doubt, DR explore unidentified cellular pathway, turning them into target for the unexplored therapeutic strategy to available molecules which were not even under clinical trial. This book chapter is a unique and only compact reference to the researcher who are involved in reprofiling existing drugs, with promising drugs, meaningful results, and conclusions on the repurposing of antiviral drugs discovery [2].
