3.5

Drug Repurposing for RNA Virus Infections

3.5.1

ZIKV and Other Flaviviruses

ZIKV is an arbovirus that leads to a large outbreak in Latin America recently.

Usually, ZIKV causes a self-limiting disease associated with neurological disorders

(such as Guillain–Barré syndrome and others). However, in the case of pregnancy,

severe congenital defects, including microcephaly and ophthalmological alterations,

have been observed in newborns. The capability of ZIKV to spread from human to

human through vertical (transplacental) and sexual transmission makes it a possible

candidate of global concern for pandemic (Wikan and Smith, 2016).

3.5.2

Ebola Virus

Since the discovery of EBOV in the late 1970s, several outbreaks have been

attributed to it. The most alarming of these outbreaks was in 2014–2016 based on

its size and spread, causing an international health emergency while being acciden-

tally imported to nonendemic geographical areas, such as Europe and the USA. The

lethal disease caused by this virus is characterized by acute hemorrhagic fever and

has fatality rate of 90%. The manipulation of EBOV for developing antiviral drugs

requires high level of biocontainment (BSL-4) that hampers the process of vaccine

development. The last outbreak of this deadly virus leads to several drug repurposing

(DR) studies (Sweiti et al., 2017; Bixler et al., 2017). A DR-based approach was

made in clinical trials amid the last outbreak of EBOV by evaluating several drugs in

infected patients for testing their ability in protecting for the lethal EBOV. These

included the viral RNA polymerase inhibitors—favipiravir (approved in Japan for

treating influenza A virus) (Sissoko et al., 2016; Liu et al., 2017), GS-5734

(an adenosine analog actively targeting highly pathogenic coronaviruses) (Warren

et al., 2016; Sheahan et al., 2017), and amodiaquine (an antimalarial drug widely

used in Africa).

3.5.3

Coronaviruses

Coronaviruses (CoVs) are RNA viruses responsible for respiratory, gastrointestinal,

and neurological diseases in animals, including zoonotic infections in humans. The

potential of these viruses of cross-species transmission is well established in

domesticated animals, which further act as intermediate hosts for infection in

humans. Severe acute respiratory syndrome CoV (SARS-CoV), a highly pathogenic

CoV, emerged in China in 2002–2003 and was responsible for causing a pandemic

with over 8098 infected people with mortality rate of 10%. Trezza et al. used a robust

in silico drug repurposing strategy to identify spike protein–ACE2 interaction

inhibitors and identified simeprevir and lumacaftor that demonstrated high binding

affinity to the receptor-binding domain of the spike protein and prevented ACE2

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A. Sharma and J. Kaur