interaction (Trezza et al., 2020). Recently, studies have demonstrated that the

repositioning of chloroquine and hydroxychloroquine for treatment of COVID-19

has proved efficacious (Khuroo, 2020; Oscanoa et al., 2020).

3.5.4

Influenza Virus

Influenza virus belonging to the family Orthomyxoviridae is a pathogen of global

public health concern as it causes seasonal, pandemic, and zoonotic influenza

disease outbreaks. The absence of innate immunity against the pandemic and

zoonotic influenza strains makes them a concern, owing to their high potential for

transmission among human population. The antiviral treatment for influenza

infections includes some options as opposed to other RNA viruses referred previ-

ously. It involves usage of adamantanes and neuraminidase inhibitors; however, the

rapid emergence of drug-resistant viral strains pose a serious challenge to this

approach (Loregian et al., 2014). DR-based approach leads to identify some previ-

ously approved drugs demonstrating anti-influenza properties, such as BAY

81-8781 (approved as intravenous aspirin), and demonstrating antiviral activity via

blockage of NF-kB pathway activation (Droebner et al., 2017), such as dapivirine

(a non-nucleoside inhibitor of HIV-1 retrotranscriptase (Hu et al., 2017), naproxen

(which targets influenza nucleoprotein (Lejal et al., 2013)), and the antibiotic

clarithromycin. Clarithromycin and naproxen in combination with oseltamivir

have been evaluated in phase 2b/3 clinical trial and have shown efficacy in the

treatment of severe influenza (Hung et al., 2017).

3.6

Drug Repurposing for DNA Virus Infections

Novel antiviral strategies involving DR have been directed against DNA viruses

responsible for latent, lifelong infections that can lead to high morbidity and also be

life-threatening for at-risk populations. Human cytomegalovirus (HCMV), a

β-herpes virus, causes persistent infection, and in immunosuppressive individuals

it can also reactivate (Mercorelli et al., 2016). Several approved or investigational

drugs have been identified using DR-based approach for the treatment of HCMV

infections that work on different anti-HCMV mechanisms (Gardner et al., 2015;

Mercorelli et al., 2016), such as the statins (Ponroy et al., 2015), cardiac glycosides

(Kapoor et al., 2012), the antiparasitic drugs emetine and nitazoxanide (Mercorelli

et al., 2016; Mukhopadhyay et al., 2016), kinase inhibitors (Arend et al., 2017), and

the antihypertensive drug manidipine (Mercorelli et al., 2018). Identification of

inhibitors for hepatitis B virus (HBV) using DR campaign identified calcium-

channel blockers, antifungal terbinafine, and dopamine receptor antagonist as

promising candidates as inhibitors of HBV RNA transcription and DNA synthesis

(van de Klundert et al., 2016). Virus-targeting drugs such as HIV integrase

inhibitors, demonstrating broad-spectrum activity against various herpesviruses by

causing the inhibition of the viral terminase (Nadal et al., 2010; Yan et al., 2014), and

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