Treatments available or under development
Since the outbreak had dealt substantial damage to the society in the
whole world, lots of scientists had started to focus on seeking a viable
solution to deal with the disease. Up to now, a considerable number of
drugs had already under development and even started the clinical trial.
Drugs reported to be effective
Since SARS-CoV-2 belongs to the betacoronavirus, therefore, it is
reasonable to use drugs used to treat SARS and MERS to inhibit the
infection of the novel virus as four key enzymes in the life cycle as
well as the Spike protein of the viruses are similar. Those proteins are
considered promising targets for drugs.(Clercq, 2020) Whist, some other
broad-spectrum antiviral drugs were also reported to be effective (Table
1).
Remdesivir,
is an adenosine analogue, an antiviral drug that against a wide range of
RNA viruses (includes SARS/MERS(Sheahan et al., 2017)) in both culture
cells and animal models, is initially an experimental antiviral drug
that treats Ebola, is now under the cooperation of Gilead Sciences Inc.
with researchers and clinicians in China. It can cause the RNA chains of
the viral to terminate before it gets to its mature stage and therefore
fulfills its antiviral function.(Warren et al., 2016) A study by Wang et
al.(M. Wang et al., 2020) had shown that Remdesivir can effectively
suppress the infection of the virus in the highly sensitive human cell
line (human liver cancer Huh-7 cells). From their detection, Remdesivir
functions one stage after the virus entry.(M. Wang et al., 2020) The
EC90 value of Remdesivir in against the SARS-CoV-2’s
infection of E6 cells was 1.76μM. Whist, the EC50 value
is 0·77μM(SI > 129.87).(M. Wang et al., 2020) Currently,
phase III clinical trials of Remdesivir have been launched in China. In
America, the first case of SARS-CoV-2 patient had been treated with
Remdesivir, and now had already been cured.(Holshue et al., 2020) Also,
in France, a patient was also treated with Remdesivir and also
cured.(Dealmoon, 2020) But further trials are still needed as there are
only a few experiments on monkey model in treating MERS but not the
SARS-CoV-2.(Dealmoon, 2020)
Chloroquine,
is a cheap drug with a long history that until recently been reported to
have a broad-spectrum antiviral capability as well as immune-modulating
activity(Savarino, Di Trani, Donatelli, Cauda, & Cassone, 2006; M. Wang
et al., 2020; Yan et al., 2013). It is originally used to treat malarial
and autoimmune disease and it is currently under evaluation in an open
trial (ChiCTR2000029609). Chloroquine inhibits virus’s infection of the
cells by escalating the endosomal PH that is essential for virus/cell
fusion, and in the meanwhile, it interferes with the glycosylation of
the SARS-viruses’ receptors.(Vincent et al., 2005) The result of the
study by Wang et al. displayed that the drug functions at both the entry
and post-entry stages of the virus invasion into the cells.(M. Wang et
al., 2020) Moreover, it was reported to be widely spread in the whole
body, including the lung.(M. Wang et al., 2020) The EC90value of Chloroquine in against the SARS-CoV-2’s infection of E6 cells
was 6·90μM, whereas the EC50 value is
1·13μM(SI > 88·50).(M. Wang et al., 2020) So far, more than
100 patients had been used Chloroquine Phosphate to treat the disease,
there have been no drug-related, obvious adverse reactions. Since it had
been used for more than 70 years in treating other diseases, experts are
considered it controllable and safe to enlarge the treatment to a wider
population.(YSA, 2020)
Hydroxychloroquine, is a
4-aminoquinoline derivative antimalarial drug. Its action and mechanism
are similar to Chloroquine, but its toxicity is only half that of
Chloroquine. Medical doctors from Wuhan University People’s Hospital
found that all the patients in their hospital with systemic lupus
erythematosus weren’t infected with the SARS-CoV-2. Hence, they suspect
that this effect may be argued by the long-termed administration of the
Hydroxychloroquine
to treat systemic lupus erythematosus, which helps in prevention of the
infection. It seems reasonable and plausible explanation since
Hydroxychloroquine has similar treating effect as Chloroquine does, and
Chloroquine, as mentioned above, was reported to be effective in
treatment of SARS-CoV-2. Therefore, they had treated 20 cases of the
patients by using Hydroxychloroquine and found that the clinical
symptoms were improved significantly in one to two days. Review of chest
CT after five days of the drug use showed a significant improvement in
the absorption in 19 cases. The remaining patient (previously had renal
insufficiency) had progressive lesions in the chest CT, but the
patient’s clinical symptoms improved significantly on the second day of
Hydroxychloroquine use. In addition, none of the normal patients
enrolled in the group developed severe illness, and one of them was
discharged/ released on February 13.(Publish, 2020) This result had
preliminary confirmed a short-term efficacy of Hydroxychloroquine in the
treatment of new coronary pneumonia, which can effectively relieve
symptoms, reverse the rate of exacerbation, and shorten the course of
the disease. Further application trials of Hydroxychloroquine in severe
and critical neo-coronary pneumonia are ongoing.
Favipiravir, is a guanine analog approved for the treatment of
influenza, which effectively inhibits the RNA-dependent RNA polymerase
of RNA viruses. A recent study reported its activity on
SARS-CoV-2.(Clercq, 2020; M. Wang et al., 2020) A randomized trial of
Favravavir in combination with interferon-α (CHICTR090029) and
barbiturvir (CHICTR09009554) for SARS-CoV-2 has been conducted.(Clercq,
2020)
Besides, Chinese traditional medicine (TCM), also known as Chinese herb,
was also reported to play a key role in treating the disease.(Hongzhuan,
2020) According to statistics, as of 00:00 on February 5th, the four
pilot provinces used TCM to treat 214 confirmed cases had shown an over
90% rate of effective, of which the symptoms of 60% of patients
experienced significant improvement, 30% of patients with stable
symptoms without exacerbation.(Ping;, 2020)