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Nature Publishing Group

Virol Sin. 2020 Feb 11 : 1–3. PMCID: PMC7090748

doi: 10.1007/s12250-020-00204-7 [Epub ahead of print]

Old Weapon for New Enemy: Drug Repurposing for Treatment of Newly
Emerging Viral Diseases
Deyin Guo

The Centre for Infection and Immunity Studies, School of Medicine, Sun Yat-sen University, Guangzhou,
510080 China
Deyin Guo, Email: [email protected].
Corresponding author.

Received 2020 Jan 29; Accepted 2020 Jan 31.

Copyright © Wuhan Institute of Virology, CAS 2020

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary
analysis in any form or by any means with acknowledgement of the original source. These permissions are granted
for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

Emerging and re-emerging viral diseases are a public health concern for the whole world and pose a
major threat to human health and life. In last decades, numerous major outbreaks of emerging and re-
emerging viral diseases with gross public concern were recorded in different regions, including Ebola in
western Africa, Zika in South America, H7N9 in China and many Asian countries, and H1N1 influenza
worldwide. In particular, coronaviruses were once regarded as the ones that just cause mild symptoms
like common cold, but three new types of coronaviruses, which emerged in the 21st century, can cause
severe diseases with high fatality and morbidity. Severe acute respiratory syndrome (SARS)
coronavirus (SARS-CoV) emerged in November 2002 in Guangdong, China and caused globally 8098
human infections with 774 deaths (9.6%), and the Middle East respiratory syndrome (MERS)
coronavirus (MERS-CoV) emerged in 2012 in Saudi Arabia and caused 2494 infections with 858
associated deaths (34.4%) as of November 2019 (WHO 2020a, b).

In December 2019, a dozen of patients with unusual pneumonia were hospitalized in Wuhan in central
China, and the causative agent was identified as a new type of coronavirus (Zhu et al.2020; Huang et
al.2020). The new virus was temporarily named as 2019 novel coronavirus (2019-nCoV) by the World
Health Organization (WHO). As of January 29, 2020, 7736 confirmed cases of 2019-nCoV infection
with 170 deaths were reported in China, and additional 77 cases in other 16 countries (National Health
Commission of the People’s Republic of China 2020; WHO 2020c). Since the emerging viruses are
previously unknown pathogens, there are no specific and effective drugs available. Therefore, there is
an urgent need for antiviral treatment in fighting the emerging viral diseases. However, the development
of antiviral drugs is time- and resource-consuming, and thus repurposing of existing drugs to treat
emerging viral diseases represents one of efficient strategies for drug development.

In a very recent work by a research team led by Drs. Gengfu Xiao, Wu Zhong and Zhihong Hu, the
antiviral efficiency of the FDA-approved drugs including ribavirin, penciclovir, nitazoxanide,
nafamostat, chloroquine (CQ) and two well-known broad-spectrum antiviral drugs remdesivir (RDV,
GS-5734) and favipiravir (T-705) were evaluated against a clinical isolate of 2019-nCoV in a cell
culture infection model (Wang et al.2020). The authors found that two compounds CQ (EC50 value = 
1.13 µmol/L; CC50 > 100 µmol/L, SI > 88.50) and RDV (EC50 = 0.77 µmol/L; CC50 > 100 µmol/L; SI 

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> 129.87) potently blocked virus infection at low-micromolar concentration and showed high selectivity
index (SI). From the in vitro results, these two compounds appear promising to be transformed into
clinical drugs for treatment of 2019-nCoV infections.

RDV is an adenosine analogue prodrug and can be incorporated into nascent chains of viral RNA,
resulting in pre-mature termination of RNA synthesis. RDV has been shown to possess a potent and
broad-spectrum antiviral activity against a diverse panel of RNA viruses such as SARS-CoV, MERS-
CoV, Ebola virus (EBOV), Marburg virus, Nipah virus, Hendra virus, and respiratory syncytial virus in
cell culture and mouse infection models (Warren et al.2016; Sheahan et al.2017; Lo et al.2017).
Currently, it is in clinical trials to evaluate its efficacy against Ebola virus infections. The study by
Wang et al. (2020) extends its antiviral activity to the new deadly coronavirus 2019-nCoV. However,
RDV has not been used in any clinical treatment, and the clinical effectiveness and safety needs to be
further investigated.

Remarkably, CQ was identified as a potent inhibitor against 2019-nCoV in cell culture infection model
(Wang et al.2020). CQ, a weak base 4-aminoquinolone derivative, has been used as a standard
antimalarial drug for more than half a century for its rapid schizonticidal activity against all malarial
parasite infections. CQ also has anti-inflammatory properties and has been approved for the clinical
treatment of autoimmune diseases such as lupus erythematosus and rheumatoid arthritis (Rainsford et
al.2015). Recently, CQ has been proven to have a broad-spectrum antiviral activity against a panel of
viruses, including SARS-CoV, MERS-CoV, EBOV, influenza A virus, Chikungunya virus, human
immunodeficiency virus, dengue virus, West Nile virus, Crimean Congo hemorrhagic fever virus, and
hepatitis A virus (García-Serradilla et al.2019). It is not surprising that CQ can suppress the infection of
a diverse group of viruses. CQ can efficiently enter the cells and accumulate in acidic compartments
like lysosomes, endosomes and trans-Golgi network vesicles, consequently raising their pH value while
many viruses need the acidic endocytic organelles at some stages of their replication, such as viral
uncoating and cellular entry via membrane fusion. CQ is also able to impair the maturation of viral
proteins and post-translational modification viral receptors like ACE2 for SARS-CoV by inhibition of
pH-dependent enzymes such as proteases or glycosyltransferases (Savarino et al.2003).

In view of its antiviral activity to SARS-CoV and MERS-CoV, it is not unexpected that CQ possesses
an antiviral activity against 2019-nCoV. However, this finding is clinically important and timely as the
2019-nCoV is currently spreading rapidly in China and causing severe respiratory diseases and deaths
of many patients. As CQ is the first-line drug for the treatment of malaria and other illnesses with a
proven safe record for several decades, it most likely represents the best candidate to be applied and
evaluated immediately in the clinical treatment of acute 2019-nCoV infections. For benefits of 2019-
nCoV patients, it is suggested that the potential clinical use of CQ be exploited and its efficacy
evaluated during the 2019-nCoV epidemics. All the repurposed uses of CQ in the treatment of viral
diseases should comply with the regulations of the administrative authorities and medical ethics.
Although CQ belongs to the safest antimalarial drugs ever discovered, adverse effects of CQ alone or in
combination with other drugs were also observed among some patients, who showed mild symptoms
such as dizziness, nausea and diarrhoea (Chattopadhyay et al.2007). In rare occasions, long-term use of
CQ may be associated with neuromyopathy and retinopathy (Chattopadhyay et al.2007). CQ is
considered safe for use during pregnancy, but its administration is contraindicated in patients with
known hypersensitivity, severe renal and hepatic diseases, a history of epilepsy, and psoriasis.
Therefore, when used in the control of viral diseases, contraindication of CQ should be taken into
account by evaluation of the physical condition, underlying diseases and comorbidities of the patients. It
is hoped that CQ and many other approved clinical drugs can be repurposed to the antiviral treatment of
emerging viral diseases that do have other effective antiviral treatment.

Acknowledgements
The author was supported by the Natural Science Foundation of China (Grant #81620108020),
Shenzhen Science and Technology Program (Grant No. KQTD20180411143323605) and Guangdong

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Provincial “Zhujiang Talents Program” (2017).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

This article does not contain any studies with human or animal subjects performed by the author.

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