Abstract
SARS-CoV-2 has been marked as a highly pathogenic coronavirus of
COVID-19 disease into the human population, causing over 2.8 million
confirmed cases worldwide. As COVID-19 has posed a global threat with
significant human casualties and severe economic losses, there is a
pressing demand to further understand the current situation and develop
rational strategies to contain the drastic spread of the virus. Although
there are no specific antiviral therapies that have proven effective in
randomized clinical trials, currently, the rapid detection technology
along with several promising therapeutics for COVID-19 have mitigated
its drastic transmission. Besides, global institutions and corporations
have commenced to parse out effective vaccines for the prevention of
COVID-19. Herein, the present review will give exhaustive details of
extensive researches concerning the drug discovery and therapeutic
options for COVID-19 as well as some insightful discussions of the
status of COVID-19.
Key word: coronavirus, COVID-19, SARS-CoV-2, precise prevention
and control, drug discovery, vaccine development
Introduction
This century has witnessed the worldwide spread of several hitherto
unknown coronaviruses. The rapid alteration of ecology and urbanization
along with vulnerable public health systems have facilitated more
frequent emerging of epidemics, which have become more and more
intractable for us to prevent and contain. In December 2019, a new
coronavirus correlated with human respiratory disease was firstly
reported causing pneumonia and death (Chan et al., 2020b). Soon
afterward, the disease cases continued to expand and soared dramatically
worldwide. The causative virus, named as SARS-CoV-2, was identified as
the pathogen leading to the coronavirus disease COVID-19. Infections
with SARS-CoV-2 are now swift and violent, and as of 26 April 2020, over
2.8 million cases have been confirmed in more than 207 countries, with
over 193,825 deaths. To date, SARS-CoV-2 has most closest relation to
SARS and relevant viruses that circulate in bats, as evidenced by viral
genome analysis as well as the research probing into the proximal origin
of such virus (Andersen et al., 2020).
In general, coronaviruses (CoVs), subfamily Coronavirinae, are a cluster
of highly diversified, enveloped, positive-sense, single-stranded
viruses ((+)ssRNA virus) that can induce enteric, respiratory, hepatic
as well as neurological disorders of discrepant severity in a wide range
of animal species, encompassing humans (Chan et al., 2013; Zumla et al.,
2016). As the largest RNA viruses ever discovered, CoVs can be
categorized into α-, β-, δ- and γ-coronaviruses. Among these genera, the
β group can be subdivided into A, B, C, and D lineages (Xia et al.,
2020b). In the past 17 years, three neoteric β-CoVs, severe acute
respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome
CoV (MERS-CoV), along with SARS-CoV-2 have emerged, engendering severe
human diseases. Although the origin of the SARS-CoV-2 outbreak is not
yet clear, recent studies have deduced that it might be transmitted
through bats because it is highly similar to the bat SARS-CoV-like
coronaviruses (Zhou et al., 2020b). Later on, genomic and evolutionary
proofs of the occurrence of Pangolin-CoV indicated that pangolin species
might be the potential intermediate host for SARS-CoV-2 (Cyranoski,
2020; T. Zhang et al., 2020). Unlike human coronaviruses, zoonotic
viruses hold the capacity of infecting both animals and humans, leading
to severe respiratory diseases (i.e., acute respiratory distress
syndrome (ARDS) and pneumonia)(Graham et al., 2013; Peiris et al.,
2003). Clinical data revealed that the COVID-19 symptoms are far more
severe among the elders with comorbidities, while asthma, allergic
illnesses, as well as chronic obstructive pulmonary disease are also
risk factors (X. Yang et al., 2020; J. Zhang et al., 2020). Despite the
continuous improvement of the prevention strategy and the disease
surveillance system, the lack of efficacious drug treatment and
correlated high morbidity cases of the SARS-CoV-2 along with its
potentiality to induce pandemics, highlighting the urgent demand for
neoteric drug discovery. In this review, we will first briefly describe
the status of epidemiology, mechanism, and diagnosis of COVID-19. In
addition to the discussion of current management strategies for
COVID-19, the emphasis has been given to the treatment options and drug
discovery of COVID-19. We will refer to the drug screening progress and
the development of vaccines for the COVID-19 therapy. Ultimately, we
will delineate the overarching challenges in the clinical invention of
new anti-coronavirus agents and offer some insights toward the
prevention of such disease based on the understanding of its epidemic
dynamics in real-time.
The epidemiology of COVID-19
Spread mainly through respiratory droplets or close contact, SARS-CoV-2
induced diseases has been growing dramatically in accordance with the
published data from the World Health Organization (WHO) (Organization,
2020). Although the number of confirmed cases in China has decreased a
lot from late February 2020, and there is no report of COVID-19 deaths
on 6 April, the confirmed cases of coronavirus worldwide are still
expanding with a vengeance. The spectrum of illness presentation or
severity profile also affects triage and diagnostic decision-making,
along with the therapeutic options and prognostic expectations (Wu et
al., 2020c). Till now, the exact source of the current outbreak of
COVID-19 remains unclear, but the dynamic model is similar to the
classic zoonotic emergence to human-to-human transmission (Metcalf and
Lessler, 2017). The mortality rate of SARS-CoV-2
(~3.8%) is lower compared to that of MERS-CoV (37.1%)
or SARS-CoV (10%), but the number of infections is more than ten times
higher (Ahn et al., 2020). With respect to the lack of evidence that
companion animals might be a source of infection, patients with COVID-19
are the prime source of infection, and those with severe conditions are
more infectious than those with mild conditions. Intriguingly,
asymptomatically infected persons or patients in incubation has also
been demonstrated to shed the infectious virus, serving as a potential
infection source to drive the transmission of the COVID-19 (Hoehl et
al., 2020). In addition, researches focused on the follow-up of
recovered patients revealed that the tested samples of rehabilitees
continuously showed a positive RT-PCR result, implicating that
asymptomatic infection during incubation or recovery from COVID-19 may
pose a daunting challenge to disease control and prevention (Lan et al.,
2020).
The incubation period refers to the time between exposure to the virus
and initial symptoms. A research report on the early propagation
dynamics of COVID-19 unveiled that the average incubation period of
COVID-19 was around 5 days, and its 95% distribution was 12.5 days (Li
et al., 2020). Another study analyzing the travel history and symptoms
in 88 confirmed cases revealed a similar average incubation period of
around 6 days (Backer et al., 2020). In addition, there was an unusual
case with an incubation period of up to 19 days (Bai et al., 2020).
Although such a long incubation period may be a low probability event
(the condition of 14 days was suggested by experts for quarantine), the
longer incubation time indicates the adjustment of screening and control
policies (Jiang et al., 2020).
The early outbreak data of COVID-19 largely follow exponential growth.
Disparate models based upon the clinical progression of the disease had
been proposed to assess the basic reproductive ratio R0.
A retrospective analysis of the first 425 identified cases demonstrated
that in the early stages of COVID-19, the R0 was
assessed to be 2.2 (Li et al., 2020). Nevertheless, deterministic
compartmental models based upon the likelihood and a model analysis
revealed that the control reproduction number Rc might
be as high as 6.5 due to the estimation of four generations of viral
transmission and serried social contacts (Tang et al., 2020). In this
regard, it is noteworthy that R0 estimates may vary in
the light of numerous biologics, social behavior, and environmental
factors (Delamater et al., 2019). In general, the basic
R0 assessed by the majority of researches ranges between
2 to 4 (Lai et al., 2020). According to the WHO data updated on April
26, 2020, more than 200 countries have reported 2,810,325 confirmed
cases, including 193,825 deaths (Figure 1). The grand total case
fatality rate of global cases outside China is 2.39% (WHO, 2020). The
US had also recorded the largest number of coronavirus deaths in a day,
with more than 1,810 deaths reported on April 7, according to data from
Johns Hopkins University. Given the condition that the population of all
races and ages is generally susceptible, there is an urgent need to
further implementing the timely diagnosis, along with efficient
isolation of patients, to cut down the R0 of SARS-CoV-2
and control the epidemic outbreak.