Therapeutic options of SARS-COV-2:
- Antiviral drugs
- Remdesivir:
Remdesivir, a monophosphate prodrug that metabolized to an active
C-adenosine nucleoside triphosphate analogue, is shown to be the most
promising and hopeful anti-viral therapeutic
(Al-Tawfiq et al., 2020). The active
metabolite of remdesivir works by targeting viral (RdRp) while evading
proofreading by viral exoribonuclease, resulting in premature
termination of viral transcription
(Al-Tawfiq et al., 2020). In a cohort
study of hospitalized patients for severe COVID-19 who were treated with
remdesivir, the clinical enhancement was observed in 68% of patients
(Grein et al., 2020).
Favipiravir
A guanine analogue prodrug, selectively inhibits RNA-dependent RNA
polymerase, has been approved to be effective in the treatment of
influenza and Ebola viruses. Favipiravir acts as a substrate of viral
RNA polymerase and halting viral replication
(Wang et al., 2020). Lately, clinical
studies have demonstrated Favipiravir to have promising influence in
treatment of Chinese patients with SARS-CoV-2 infection in terms of
disease development and viral clearance
(Cai et al., 2020).
Lopinavir/ritonavir
Lopinavir/Ritonavir is a combination of antiretroviral protease
inhibitors used in contemporary treatment of chronic human
immunodeficiency virus infection (Sanders
et al., 2020). Ritonavir is combined with Lopinavir to increase its
half-life of Lopinavir via inhibition of cytochrome P450. Several
retrospective and non-randomized cohort studies ascertain that
Lopinavir/Ritonavir could inhibit SARS-CoV-2 replication in lung (Kumar
et al., 2020; Yao et al., 2020). However,
a recent study has noticed that the efficacy of Remdesivir was superior
to that of Lopinavir/Ritonavir (Sheahan et
al., 2020).
Umifenovir (Arbidol):
Arbidol is a non-nucleoside antiviral and immunomodulating agent that
was commonly used for influenza treatment in Russia and China. For
SARS-CoV-2, Umifenovir can potentially target S protein/ACE2 interaction
and inhibit membrane fusion of the viral envelope
(Sanders et al., 2020). A clinical study
showed that Umifenovir could accelerate and enhance the process of viral
clearance, improve chest radiologic images, and reduce the demand for
oxygen therapy in hospitalization (Xu et
al., 2020). However, the drug is only available in few countries.
Monoclonal Antibodies (Sarilumab and Tocillzumab)
It was demonstrated that SARS-CoV-2 is associated with “Cytokine
storm” in which release of large amounts of inflammatory cytokines such
as interleukin-6 (IL-6) occur. The increased pulmonary inflammatory
response may result in increased alveolar-capillary gas exchange, making
oxygenation difficult in patients with severe illness
(Coperchini et al., 2020). Interleukin-6
inhibitors may ameliorate severe damage to lung tissue caused by
cytokine storm in patients with serious COVID-19 infections
(Zhang et al., 2020b).
Sarilumab and Tocillzumab are IL-6 receptor blockers used for treatment
of rheumatoid arthritis (June and Olsen,
2016). Both drugs are associated with serious infections rendering the
patients at risk of death from these serious infections. In addition,
Tocillzumab may cause rare but serious cases of liver injury, and in
some cases liver transplantation may be required
(June and Olsen, 2016). Sarilumab had an
off label use to act against severe advanced cases of COVID-19, however,
the drug is still under clinical investigation without any current
approval from FDA (Sanofi, 2020). Chinese
trial found that COVID-19 patients experienced rapidly reduced fever and
lower need for supplemental oxygen within days of receiving Tocillzumab
(Campochiaro et al., 2020). China recently
updated its COVID-19 treatment guidelines and approved the use of IL-6
inhibitors to treat patients with severe or critical disease and who
developed cytokine storm (Sanofi, 2020).
Anticoagulants:
Coagulopathy was found in a significant number of COVID-19 non
survivors. Coagulation laboratory tests are essential to be known for
all COVID-19 patients (e.g: D-dimer, prothrombin time, and platelet
count). It is considered that anticoagulant therapies is accompanied
with decreased mortality in severe COVID-19 patients
(Tang et al., 2020). The use of heparin
(Low molecular weight heparin LMWH or unfractionated heparin UFH) has
potential benefit over other anticoagulants due to its anticoagulant,
anti-inflammatory and potentially anti-viral properties and its effects
against ARDS (Shi et al., 2020). A
retrospective clinical study has demonstrated the use of low molecular
weight heparin as potential therapeutic agent for treatment of COVID-19
through mitigate the cytokine storm (Shi
et al., 2020). Furthermore, LMWH or UFH are preferred in critically ill
patients because of their shorter half-lives and fewer drug-drug
interactions compared with oral anticoagulants
(Tang et al., 2020).
Hydroxychloroquine:
Hydroxychloroquine is an
antimalarial
agent and used in treatment of
rheumatoid arthritis and
systemic lupus erythematosus. It blocks viral entrance into cells by
inhibiting glycosylation of host receptors, endosomal acidification, and
proteolytic processing. Moreover, has immunomodulatory effects through
inhibition of cytokine production, autophagy, and lysosomal activity in
host cells (Devaux et al., 2020). It has
been reported that co-administration of azithromycin with
hydroxychloroquine in resulted in superior virologic clearance in
comparison with hydroxychloroquine monotherapy
(Gautret et al., 2020).
Hydroxychloroquine may cause rare but dangerous adverse effects,
including retinopathy, hypoglycemia, and neuropsychiatric effects and
further clinical trials are required to detect the safest and most
effective dose required for the clearance of the new virus
(Kalil, 2020).
Convalescent plasma (CP) therapy:
Objectives reports for convalescent plasma have been stated as salvage
therapy in severe acute respiratory syndrome (SARS) and pandemic
influenza H1N1. Plasma from recovered COVID-19 patients contains large
quantity of antibodies capable of neutralizing SARS-CoV-2 and
eradicating the pathogen from blood circulation and pulmonary tissues
(Cantore and Valente, 2020). In the
meantime, clinical symptoms and radiological examination rapidly
improved within 7 days (Duan et al.,
2020). However, the administration of CP may need more randomized
clinical trials to compare the outcomes of treatment group with control
one and to ensure the clinical benefits alone or in combination with
other drugs.
- Miscellaneous agents
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