These studies collectively suggest that the FDA approved anti-HIV therapeutic candidates should be considered more actively for additional applications not only for other viruses but also non-infectious diseases such as cancer. 4. In this review, we discuss in detail the drug repurposing approach and its advancements related to viral infections such as Human Immunodeficiency Virus (HIV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). family to a substantial extent. Hence, molecules that inhibit HIV-1 replication would likely inhibit other retroviruses and vice versa. Since the approval of the first anti-HIV medicine, the development of novel anti-HIV therapeutics has erupted including novel chemical entities and structures with significant anti-HIV activities. Not only are these novel formulations used for their anti-HIV activity, but also studied for their different therapeutic implications including various types of cancers. In the late 1990s, the HIV-1 reverse transcriptase inhibitors (RTIs) were highlighted in several reports and demonstrated very efficient anti-HIV activity. Along with the drastic decline in the free circulating viral load, patients treated with RTIs were also observed to have a gradual increase in their CD4+ T-cell counts and, more importantly, the treatment also helped control Kaposis Sarcoma (KS) [47]. These observations gave the first indications of possible anti-cancer activity of RTIs. RTIs are nucleotide analogs, which hamper cellular DNA synthesis thus inducing cell death even in uninfected cells at high concentrations. For example, cidofovir and ganciclovir have been widely investigated for their ability to induce cell death in rapidly dividing cancer cells [48,49,50]. Efavirenz has been demonstrated to have profound antiproliferative activity against pancreatic cancer as well as anaplastic thyroid cancer [51]. Rilpivirine was recently shown to block Zika virus infection in the brain along with etravirine and efavirenz [52]. However, other FDA approved drugs and investigational RT inhibitors have not been well studied for their anti-cancer activity. Hence, we believe that several of these HIV-1 RT inhibitors should be investigated further for their anti-cancer activities, which may aid in the development of more efficient therapeutic strategies against various incurable cancers. Further, the introduction of HIV-1 protease (PR) inhibitor, saquinavir, Midodrine in December 1995, opened a horizon of opportunities for studying its application not only as an anti-HIV agent, but also anti-cancer and anti- inflammatory agent. Apart from their anti-cancer activity, HIV-1 protease inhibitors such as ritonavir and lopinavir are documented to have anti-protozoal activity at micromolar to nanomolar concentrations [53]. Further, these inhibitors have been reported Midodrine to have anti-malarial activity [54] and also shown to cure Chagas diseases [55]. However, these Rabbit Polyclonal to CK-1alpha (phospho-Tyr294) protease inhibitors demonstrated off-target effects, which have consequently limited their use as medications at various phases of clinical trials for several other diseases. Midodrine Most recently, the use of anti-HIV PR inhibitors has shown new hope in the development of effective treatment against the novel SARS-CoV-2 infection (COVID-19). Previously, ribavirin, lopinavir in combination with ritonavir demonstrated significant anti-viral potential against SARS as well as MERS associated coronaviruses [56]. As an extension of these observations, remdesivir was Midodrine recently tested for its antiviral activity against SARS-CoV-2 in vitro and was found to block virus replication at nanomolar concentration [57]. Additionally, remdesivir also demonstrated strong inhibitory potential against a range of viruses including Filoviruses such as Ebola [58,59,60]. These studies collectively suggest that the FDA approved.