Int. J. Biol. Sci. 2020, Vol.

16 1678

Ivyspring
International Publisher
International Journal of Biological Sciences
2020; 16(10): 1678-1685. doi: 10.7150/ijbs.45053
Review

SARS-CoV-2: an Emerging Coronavirus that Causes a

Global Threat
Jun Zheng1,2
1. Faculty of Health Sciences, University of Macau, Macau SAR, China.
2. Institute of Translational Medicine, University of Macau, Macau SAR, China.

 Corresponding author: Jun Zheng, [email protected].

© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
See http://ivyspring.com/terms for full terms and conditions.

Received: 2020.02.18; Accepted: 2020.02.28; Published: 2020.03.15

Abstract
An ongoing outbreak of pneumonia caused by a novel coronavirus, currently designated as the
severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was reported recently. However,
as SARS-CoV-2 is an emerging virus, we know little about it. In this review, we summarize the key
events occurred during the early stage of SARS-CoV-2 outbreak, the basic characteristics of the
pathogen, the signs and symptoms of the infected patients as well as the possible transmission
pathways of the virus. Furthermore, we also review the current knowledge on the origin and
evolution of the SARS-CoV-2. We highlight bats as the potential natural reservoir and pangolins as
the possible intermediate host of the virus, but their roles are waiting for further investigation.
Finally, the advances in the development of chemotherapeutic options are also briefly summarized.
Key words: Coronavirus, Novel coronavirus, pneumonia, SARS-CoV-2, COVID-19

Introduction
On 23 Feb 2020, the lock-down of Wuhan, a coronavirus causing severe acute respiratory
central city in China, has alarmed people all over the syndrome (SARS-CoV) in late of 2002 [3-6]. Currently,
world of an emerging novel coronavirus that is posing at least seven coronavirus species are known to cause
a major public health and governance challenges. The diseases in humans. The viruses of 229E, OC43, NL63
novel virus, previously called the 2019-novel and HKU1 only cause common cold symptoms,
coronavirus (2019-nCoV), is currently designated as which are mild. Severe illness can be caused by the
the severe acute respiratory syndrome coronavirus-2 remaining three viruses, namely SARS-CoV, which
(SARS-CoV-2). As of 27 Feb, this emerging infection resulted in the outbreak of SARS in 2002 and 2003
has been reported in 47 countries, causing over 82,294 [3,4]; the coronaviruses that are responsible the
infections with 2,804 deaths (Fig. 1) [1]. This novel Middle East respiratory syndrome (MERS-CoV),
virus is also becoming a mounting threat to Chinese which emerged in 2012 and remains in the circulation
and global economies. in camels [7]; and SARS-CoV-2, the viruses emerged
Coronaviruses (CoVs) are members of the family in December 2019 in Wuhan of China and a great
Coronaviridae, the enveloped viruses that possess effort is being undertaken to contain its spreading [8].
extraordinarily large single-stranded RNA genomes In this review, we will briefly introduce the outbreak
ranging from 26 to 32 kilobases in length [2]. CoVs history of SARS-CoV-2, the signs and symptoms of
have been identified in both avian hosts and various the infected patients, its transmission dynamics, the
mammals, including bat, camels, dogs and masked advances in the understanding on its evolutional
palm civets, and are previously regarded as origin and the chemotherapeutic options being
pathogens that only cause mild diseases in the developed for the treatment of its infection.
immunocompetent people until the emergence of the

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Int. J. Biol. Sci. 2020, Vol. 16 1679

Figure 1. Key events in the early stage of SARS-CoV-2 outbreak.

with deep sequencing [8,14-18]. The viral genome of

The key events of SARS-CoV-2 outbreak and SARS-CoV-2 is around 29.8 kilobase, with a G+C
the pathogen characteristics content of 38%, in total consisting of six major open
Since December 2019, an increasing number of reading frames (ORFs) common to coronaviruses and
patients with pneumonia of unknown etiology in a number of other accessory genes [14,16]. The
Wuhan, a city with 11 million people, have alarmed sequences analysis showed that the genome
the local hospital. On 29 December 4 cases were sequences of viruses from different patients are very
linked to Huanan Seafood wholesale market [9], conserved [14,15,19], implying that the human virus
where non-aquatic live animals, including several evolves recently.
kinds of wild animals, were also on the sales. The
local Center for Disease Control (CDC) then found Signs and symptoms of patients infected by
additional patients linked to the same market after SARS-CoV-2
investigation, and reported to China CDC on 30 Dec A typical characteristic of the SARS-CoV-2
2019 [9]. The second day, World Health Organization infected patient is pneumonia, now termed as
(WHO) was informed of the cases of pneumonia of Coronavirus Disease 2019 (COVID-19), demonstrated
unknown etiology by China CDC [10]. On 6 Jan 2020, by computer tomographic (CT) scan or chest X -ray
a level 2 emergency response was launched by China [3,8,18]. In the early stages, the patients showed the
CDC [11]. acute respiratory infection symptoms, with some that
The causal agent was not identified until 7 Jan quickly developed acute respiratory failure and other
2020; a new type of coronavirus was isolated by serious complications [20]. The first three patients
Chinese authority [10]. The genome sequence of reported by the China Novel Coronavirus
SARS-CoV-2 (WH-Human_1) was first released and Investigating and Research Team all developed severe
shared by China on 10 Jan [12]. The isolation and pneumonia and two of these three patients with
identification of SARS-CoV-2 apparently facilitated available clinical profiles showed a common feature of
the development of molecular diagnostic methods fever and cough [8]. A subsequent investigation of a
and the confirmation of the infected patients. As of 21 family of six patients in the University of Hong
Jan, there are 270 cases were confirmed from Wuhan Kong-Shenzhen Hospital demonstrated that all of
[13]. On 23 Jan, Wuhan city was locked down by local them had pulmonary infiltrates, with a variety of
government. On 30 Jan, WHO declared a “public other symptoms [18]. The chest X-ray and CT imaging
health emergency of international concern” (Fig. 1). in a study showed that 75% of 99 patients
Subsequently, the viruses were successfully demonstrated bilateral pneumonia and the remaining
isolated from several laboratories [8,14,15]. The virion 25% unilateral pneumonia [21]. Overall, 14% of the
of SARS-CoV-2 looks like a solar corona by patients showed multiple mottling and ground-glass
transmission electron microscopy imaging: the virus opacity [21]. The first cases of coronavirus infection in
particle is in a spherical shape with some the United States also showed basilar streaky
pleomorphism; the diameter of the virus particles opacities in both lungs by chest radiography.
range from 60 to 140 nm with distinctive spikes about However, the pneumonia for this patient was only
8 to 12 nm in length [8]. The observed morphology of detected on the day 10 of his illness [22]. It is also of
SARS-CoV-2 is consistent with the typical note that one of patients among the family of six
characteristics of the Coronaviridae family. The patients did not present any other symptoms and
genome sequence of SARS-CoV-2 from clinical signs, but had ground-glass lung opacities identified
samples has been obtained by several laboratories by CT scan [18].

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Table 1. Common signs and symptoms of SARS-CoV-2 infected patients from four reports
Signs or Symptoms Number of patients with signs or symptoms from each report Number of patients with Total number of Percentage
Report 1 [21] Report 2 [23] Report 3 [24] Report 4 [25] signs or symptoms patients
Fever 82 (n=99) 40 (n=41) 136 (n=138) 975 (n=1099) 1233 1377 90%
Cough 81 (n=99) 31 (n=41) 82 (n=138) 745 (n=1099) 939 1377 68%
Sputum production/ NR 11 (n=39) 37 (n=138) 370 (n=1099) 418 1276 33%
Expectoration
Shortness of breath/ 31 (n=99) 22 (n=40) 43 (n=138) 205 (n=1099) 301 1376 22%
Dyspnoea
Headache 8 (n=99) 3 (n=38) 9 (n=138) 150 (n=1099) 170 1374 12%
Sore throat/Pharyngalgia 5 (n=99) NR 24 (n=138) 153 (n=1099) 182 1336 14%
Diarrhoea 2 (n=99) 1 (n=38) 14 (n=138) 42 (n=1099) 59 1374 4%
NR: Not Recorded.

another [29]. The R0 of SARS-CoV-2 from both of these

At least four comprehensive studies on the two studies is smaller than that of SRAS, which are 3
epidemiological and clinical characteristics of SARS- before public health measures were implemented
CoV-2 infected patients have been performed [21, [30]. However, subsequent investigation based on the
23-25]. The most common signs and symptoms of analysis of high-resolution real-time human travel
patients are fever and cough [21,23-25]. Fatigue was and infection data estimated that the R0 is much
complained by 96% of patients (n=138) in one study larger, ranging from 4.7 to 6.6 before the control
[24], but was less outstanding (18%, n=44) in another measures [31], implying that SARS-CoV-2 is highly
report [23]. A combinational analysis of the common contagious and more infectious than initially
recorded signs or symptoms of the reported cases estimated. This conclusion is consistent with the wide
found that fever was observed in around 90% of the spread of SARS-CoV-2 within a short period time and
SARS-CoV-2 infected patients; the number of patients was also echoed by the finding that SARS-CoV-2
with cough is relatively less (68%) compared to fever Spike (S) protein had 10- to 20-fold higher affinity to
(Table 1). In addition, shortness of breath or dyspnea, human angiotensin-converting enzyme 2 (ACE2)
muscle ache, headache, chest pain, diarrhea, receptor than that of SARS-CoV based on the
haemoptysis, sputum production, rhinorrhoea, Cryo-EM structure analysis of S proteins [32]. Similar
nausea and vomiting, sore throat, confusion, and to SARS-CoV, the entry of SARS-CoV-2 into host cells
anorexia were also observed in a proportion of the depends on the recognition and binding of S protein
patients [21,23-25] (Table 1). to ACE2 receptor of the host cells [14,33]. The high
A common feature of patients of SARS, MERS or affinity of S protein to ACE2 receptor likely
COVID-19 is the presence of severe acute respiratory contributes to the quick spreading of virus. The
syndrome; however, the estimated fatality rate of finding of ACE2 as the receptor of SARS-CoV-2 also
COVID-19 (2.3%) is much lower than SARS (~10%) indicates that human organs with high ACE2
and MERS (~36%) [26,27]. Furthermore, the viruses expression level, such as lung alveolar epithelial cells
responsible for above three diseases are evolutionary and enterocytes of the small intestine, are potentially
distinct (See below for details) [19]. the target of SARS-CoV-2 [34].
Transmission of the virus As a new coronavirus, it is not known yet about
how SARS-CoV-2 spreads. Current knowledge for
It is clear now that SARS-CoV-2 can be
SARS-CoV-2 transmission is largely based on what is
transmitted by human-to-human despite the majority
known from the similar coronaviruses, particularly
of the early cases had contact history with the Huanan
SARS-CoV and MERS-CoV, in which human-to-
Seafood market [11,18,28]. Analysis of 425 patients
human transmission occurs through droplets, contact
with confirmed COVID-19 showed that the
and fomites. SARS-CoV is predominantly transmitted
incubation period is 3 to 7 days. The mean was 5.2
through indirect or direct contact with mucous
days (95% CI: 4.1 to 7.0), and the 95th percentile of the
membranes in the mouth, eyes, or nose [35]. It has
distribution is 12.5 days (95% CI: 9.2 to 18) [11].
been shown that unprotected eyes and exposed
Notably, it was reported that the incubation period
mucous membranes are vulnerable to SARS-CoV
could be as long as 24 days in a rare case [25]. The
transmission [36]. A member of the national expert
basic reproductive number (R0) up to the period of 4
panel on pneumonia was infected by SARS-CoV-2
Jan 2020 was estimated based on the study of 425
after the inspection in Wuhan [37]. As he wore a N95
patients to be 2.2 (meaning that one patient has been
mask but not any eye protector, and experienced eye
spreading infection to 2.2 other people) [11], slightly
redness before the onset of pneumonia, it was thus
smaller than the value of 2.68 by a modelling in
suspected that unprotected exposure of the eyes to

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SARS-CoV-2 might be another transmission pathway with Huanan Seafood market suggested that the
[37]. However, SARS-CoV-2 was not detected from marketplace has played a role in the early spreading
the conjunctival swab sample in a confirmed COVID- [11,23], however, whether it is the origin of the
19 patent with conjunctivitis [38], suggesting that outbreak and what is the native host(s) of
more evidences are needed before concluding the SARS-CoV-2 remain uncertain. In fact, the firstly
conjunctival route as the transmission pathway of documented patient was not linked to Huanan
SARS-CoV-2. The mode of transmission by MERS- Seafood market [23].
CoV is not well understood but is believed to spread The analysis of SARS-CoV-2 origin was firstly
largely via the respiratory close contact route [39,40]. performed based on the genome sequence of virus
Based on the transmission mode of SARS-CoV isolates from six patients [19]. When compared with
and MERS-CoV, a serial of preventive measures have SARS-CoV and MERS-CoV, the nucleotide sequences
been recommended, including avoiding close contact of SARS-CoV-2 showed a higher homology with that
with people suffering from acute respiratory of SARS-CoV while was relatively poor with that of
infections and frequent hand-washing [41]. The MERS-CoV [19]. Despite some of the six major OFRs
viruses of SARS-CoV-2 were also detected in the stool of SARS-CoV-2 genes share less than 80% identity in
samples in some patients but not all [18,22], nucleotide acids to SARS-CoV, the seven conserved
suggesting that a possible fecal-oral transmission replicase domains in ORF1ab has 94.6% sequence
occurs [42]. A systematic study showed that viruses identity in amino acids between SARS-CoV-2 and
could be detected in oral swabs, anal swabs and blood SARS-CoV [14], suggesting that these two viruses
samples of the patients, and the anal swabs and blood might belong to the same species. The origin of
could test positive when oral swab tested negative SARS-CoV has been extensively investigated. Masked
[43]. Furthermore, a trend of shift from more oral palm civets were initially considered to transmit
positive in the collected samples during the early SARS-CoV to humans as a close variant of SARS-CoV
period of patient infection to more anal positive was detected from palm civets [49]. This conclusion
during later period of infection was also found [43]. was supported by the fact that three of the four
Therefore, a multiple shedding routes of SARS-CoV-2 patients had the record of contact with palm civets
might exist. during the two small-scale of SARS outbreaks
One of the challenges for preventive control of occurred in late 2003 and early 2004 [50, 51]. However,
SARS-CoV-2 spreading is that the viruses are likely a deep investigation based on the genome sequence of
transmitted by asymptomatic contact. A German isolated viruses showed that SARS-CoV-like virus in
businessman was found infected by SARS-CoV-2 after civet had not been circulating for long [52].
attending a conference together with a colleague, who Subsequently, coronaviruses with high similarity to
had no signs or symptoms of infection but had the human SARS-CoV or civet SARS-CoV-like virus
become ill due to the SARS-CoV-2 infection later [44]. were isolated from horseshoe bats, concluding the
This observation suggests that infected patients likely bats as the potential natural reservoir of SARS-CoV
start to shed viruses before the onset of any symptom, whereas masked palm civets are the intermediate host
which undoubtedly will bring great challenge to the [53-56].
current practice of preventive control by measuring It is thus reasonable to suspect that bat is the
body temperature. Despite the claim of the natural host of SARS-CoV-2 considering its similarity
transmission by asymptomatic contact has been with SARS-CoV. The phylogenetic analysis of SARS-
challenged [45], other asymptomatic carriers were CoV-2 against a collection of coronavirus sequences
also observed to transmit the viruses of SARS-CoV-2 from various sources found that SARS-CoV-2
[46,47]. Consistently, a study found that an belonged to the Betacoronavirus genera and was closer
asymptomatic patient had a similar vial loads in the to SARS-like coronavirus in bat [19]. By analyzing
samples of nasal and throat swabs to that of the genome sequence of SARS-CoV-2, it was found that
symptomatic patients [48]. SARS-CoV-2 felled within the subgenus Sarbecovirus
of the genus Betacoronavirus and was closely related
The origin and evolution of SARS-CoV-2 to two bat-derived SARS-like coronaviruses,
It is critical to identify the origin, native host(s) bat-SL-CoVZC45 and bat-SL-CoVZXC21, but were
and evolution pathway of the virus that causes an relatively distant from SARS-CoV [15, 18, 57-59].
outbreak of a pandemic. This information can help Meanwhile, Zhou and colleagues showed that
understand the molecular mechanism of its SARS-CoV-2 had 96.2% overall genome sequence
cross-species spread and implement a proper control identity throughout the genome to BatCoV RaTG13, a
measure to prevent it from further spreading. The bat coronavirus detected in Rhinolophus affinis from
association of initially confirmed SARS-CoV-2 cases Yunnan province [14]. Furthermore, the phylogenetic

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analysis of full-length genome, the receptor binding RaTG13 only possesses one [62]. The discovery of
protein spike (S) gene, and RNA-dependent RNA coronavirus close to SARS-CoV-2 from pangolin
polymerase (RdRp) gene respectively all suggests that pangolin is a potential intermediate
demonstrated that RaTG13 was the closest relative of host. However, the roles of bat and pangolin as
the SARS-CoV-2 [14]. However, despite SARS-CoV-2 respective natural reservoir and intermediate host still
showed high similarity to coronavirus from bat, need further investigation.
SARS-CoV-2 changed topological position within the
subgenus Sarbecovirus when different gene was used Chemotherapeutic options for SARS-CoV-2
for phylogenetic analysis: SARS-CoV-2 was closer to infection
bat-SL-CoVZC45 in the S gene phylogeny but felled in As an emerging virus, there is no effective drug
a basal position within the subgenus Sarbecovirus in or vaccine approved for the treatment of SARS-CoV-2
the ORF1b tree [57]. This finding implies a possible infection yet. Currently, supportive care is provided
recombination event in this group of viruses. Of note, to the patients, including oxygen therapy, antibiotic
the receptor-binding domain of SARS-CoV-2 treatment, and antifungal treatment, extra-corporeal
demonstrates a similar structure to that of SARS-CoV membrane oxygenation (ECMO) etc. [21,22]. To
by homology modelling but a few variations in the search for an antiviral drug effective in treating
key residues exist at amino acid level [15, 19]. SARS-CoV-2 infection, Wang and colleagues
Despite current evidences are pointing to the evaluated seven drugs, namely, ribavirin, penciclovir,
evolutional origin of SARS-CoV-2 from bat virus [15, nitazoxanide, nafamostat, chloroquine, remdesivir
57], an intermediate host between bats and human (GS-5734) and favipiravir (T-750) against the infection
might exist. Lu et. al. raised four reasons for such of SARS-CoV-2 on Vero E6 cells in vitro [63]. Among
speculation [15]: First, most bat species in Wuhan are these seven drugs, chloroquine and remdesivir
hibernating in late December; Second, no bats in demonstrated the most powerful antiviral activities
Huanan Seafood market were sold or found; Third, with low cytotoxicity. The effective concentration
the sequence identity between SARS-CoV-2 and (EC50) for chloroquine and remdesivir were 0.77µM
bat-SL-CoVZC45 or bat-SL-CoVZXC21, the closest and 1.13µM respectively. Chloroquine functions at
relatives in their analyses, is lower than 90%; Fourth, both viral entry and post-entry stages of the
there is an intermediate host for other human- SARS-CoV-2 infection in Vero E6 cells whereas
infecting coronaviruses that origin from bat. For remdesivir does at post-entry stage only. Chloroquine
example, masked palm civet and dromedary camels is a drug used for an autoimmune disease and
are the intermediate hosts for SARS-CoV [49] and malarial infection with potential broad-spectrum
MERS-CoV respectively [60]. A study of the relative antiviral activities [64,65]. An EC90 (6.90 µM) against
synonymous codon usage (RSCU) found that the SARS-CoV-2 in Vero E6 cells is clinically
SARS-CoV-2, bat-SL-CoVZC45, and snakes had achievable in vivo according to a previous clinical trial
similar synonymous codon usage bias, and speculated [66]. Remdesivir is a drug currently under the
that snake might be the intermediate host [61]. development for Ebola virus infection and is effective
However, no SARS-CoV-2 has been isolated from to a broad range of viruses including SARS-CoV and
snake yet. MERS-CoV [67,68]. Functioning as an adenosine
Pangolin was later found to be a potential analogue targeting RdRp, Remdesivir can result in
intermediate host for SARS-CoV-2. The analysis of premature termination during the virus transcription
samples from Malytan pangolins obtained during [69,70]. The EC90 of remdesivir against SARS-CoV-2 in
anti-smuggling operations from Guangdong and Vero E6 cells is 1.76 µM, which is achievable in vivo
Guangxi Customs of China respectively found novel based on a trial in nonhuman primate experiment [63,
coronaviruses representing two sub-lineages related 69]. Encouragingly, in the first case of SARS-CoV-2
to SARS-CoV-2 [62]. The similarity of SARS-CoV-2 to infection in the United States, treatment with
these identified coronaviruses from pangolins is remdesivir was provided intravenously to the patient
approximately 85.5% to 92.4% in genomes, lower than on the day 7 without any adverse events observed.
that to the bat coronavirus RaTG13 (96.2%) [14,62]. The patient’s clinical condition was improved on day
However, the receptor-binding domain of S protein 8 and the previous bilateral lower-lobe rales
from one sub-lineage of the pangolin coronaviruses disappeared, implying the remdesivir might be
shows 97.4% similarity in amino acid sequences to effective to the treatment of SARS-CoV-2 infection
that of SARS-CoV-2, even higher than that to RaTG13 [22]. This result, however, should be interpreted with
(89.2%) [62]. Interestingly, the pangolin coronavirus caution as this is only single case study and a proper
and SARS-CoV-2 share identical amino acids at the trial control was lacking. In addition, baricitinib, a
five critical residues of RBD of S protein, while Janus kinase inhibitor, was also predicted to reduce

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Int. J. Biol. Sci. 2020, Vol. 16 1683

the ability of virus to infect lung cell by an analysis of result in the collapse of health care system, and thus
BenevolentAI [71]. the mortality rate might be elevated. Effective
Currently, chloroquine and remdesivir are under preventive measures must be implemented to control
phase 3 clinical trial and open-label trial for treatment it from global spreading. In addition, great effort
of SARS-CoV-2 infection respectively (Table 2) [72]. should be made on the development of vaccine and
Preliminary results showed that chloroquine antiviral drugs. Meanwhile, the intermediate host and
phosphate had apparent efficacy in treatment of the molecular mechanism of its cross-species spread
COVID-19 [73]. However, caution must be taken should be further investigated. Legislation should be
during clinical use of chloroquine as its overdose is employed to prohibit the trade of wild animals, the
highly fatal without known antidote [74]. Despite the potential intermediate host(s) of various viruses, to
lack of documented in vitro data supporting the prevent the outbreak of this and other novel viruses in
antiviral efficacy on SARS-CoV-2, several antiviral future.
chemotherapeutic agents have been registered for the
clinical trials for the treatment of COVID-19 (Table 2) Acknowledgements
[72]. We acknowledge the Research Committee of the
University of Macau (Grant No.: MYRG2016-
Conclusion remarks
00073-FHS, MYRG2016-00199-FHS and MYRG2019-
SARS-CoV-2 is an emerging pathogen, without 000050-FHS) and the Macau Science and Technology
any effective drug available for treatment at the Development Fund (Grant No.: FDCT/0058/2018/A2
moment. It spreads quickly and can result in death of and FDCT/0113/2019/A2) for providing financial
the infected patients. Despite the current mortality support for this research.
rate is 2.3% [26], the emergence of large number of
infected patients within short period of time could

Table 2. Summary of chemotherapeutic drugs under clinical trial for COVID-19

Name of Drug Target and Mode of In Vitro Antiviral Clinical Trial Status Clinical Trial Registration Number
Action in other Activity to for COVID-19
Viruses SARS-CoV-2
Remdesivir (GS-5734) Inhibits RdRp [70] Tested [63] Phase 3 NCT04252664; NCT04257656

Favipiravir Inhibits RdRp [75] Tested [63] Randomized trial ChiCTR2000029544; ChiCTR2000029600

Ribavirin Inhibits viral RNA Tested [63] Randomized trial, in ChiCTR2000029387

synthesis and mRNA combination a
capping [76] pegylated interferon

Lopinavir Inhibits 3C like Not tested Phase 3 NCT04252274; NCT04251871; NCT04255017;

protease (3Clpro) [77] ChiCTR2000029539

Ritonavir Inhibits 3Clpro [77] Not tested Phase 3 NCT04251871; NCT04255017; NCT04261270

Darunavir and Cobicistat Inhibits HIV protease Not tested Phase 3 NCT04252274
[78]
ASC09F (HIV protease inhibitor) Inhibits HIV protease Not tested Phase 3, in NCT04261270
[79] combination with
oseltamivir
Chloroquine A lysosomatropic Tested [63] Open-label trial ChiCTR2000030054; ChiCTR2000029939;
base that appears to ChiCTR2000029935; ChiCTR2000029899;
disrupt intracellular ChiCTR2000029898; ChiCTR2000029837;
trafficking and viral ChiCTR2000029803; ChiCTR2000029761;
fusion events [80] ChiCTR2000029740; ChiCTR2000029559;
ChiCTR2000029542; ChiCTR2000029868;
ChiCTR2000029826; ChiCTR2000029762;
ChiCTR2000029760; ChiCTR2000029609
Arbidol (Umifenovir) Block viral fusion [81] Not tested Phase 4 NCT04260594; NCT04254874; NCT04255017

Oseltamivir Inhibit neuaminidase Not tested Phase 3 and Phase 4 NCT04255017; NCT04261270
[82]

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