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
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 > 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.
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.