Efficacy and Safety of Direct Anti HCV Drugs in the Treatment of SARS-COV-2 (COVID-19)

SARS-CoV-2 infection have a wide clinical spectrum ranging between asymptomatic infection,
mild upper respiratory tract symptoms, and severe viral pneumonia (fever, malaise, dry cough,
shortness of breath, and respiratory distress) that may result in respiratory failure and
finally death.

There is currently no clinically proven specific antiviral agent available for SARS-CoV-2
infection. Supportive treatment, including oxygen therapy, conservation fluid management, and
broad-spectrum antibiotics to cover secondary bacterial infection, remains the most important
management strategy.

For direct antiviral treatment of SARS-CoV-2, the China International Exchange and Promotive
Association for Medical and Health Care (CPAM) recommended usage of lopinavir; ritonavir.
Their recommendation was based on weak evidence from retrospective cohort, historically
controlled studies, case reports, and case series reporting a clinical benefit of lopinavir;
ritonavir in the management of other coronavirus infection [i.e., SARS-CoV 1 and Middle East
respiratory syndrome coronavirus (MERS-CoV)] .

However, the first randomized clinical trial with lopinavir/ritonavir demonstrated no benefit
over standard care in 199 hospitalized adults with severe COVID-19. There is no evidence to
support the use of other antiretrovirals, including protease inhibitors; indeed, structural
analysis demonstrates no darunavir binding to COVID-19 protease A group of Korean physicians
experienced in SARS-CoV-2 infected patients' treatment developed recommendations for the
treatment of COVID-19. According to them, antiviral medications lopinavir 400 mg; ritonavir
100 mg, or chloroquine is considered to be used in older patients or patients with chronic
health conditions and life-threatening symptoms. If chloroquine is unavailable,
hydroxychloroquine is recommended. Both of them have reported the ability of inhibition of
SARS-CoV-2 in vitro.

CPAM guidelines included them as they were associated with reduced progression of the disease
and decreased duration of symptoms. In an open-label study of 36 patients with COVID-19, the
use of hydroxychloroquine (200 mg three times per day for 10 days) was associated with a
higher rate of undetectable SARS-CoV-2 RNA on nasopharyngeal specimens at day 6 compared with
no specific treatment (70 versus 12.5 percent). In this study, the use of azithromycin in
combination with hydroxychloroquine appeared to have an additional benefit, but there are
methodologic concerns about the control groups for the study, and the biologic basis for
using azithromycin in this setting is unclear. In the United States, the FDA issued an
emergency use authorization to allow the use of these agents in adolescents or adults
hospitalized for COVID-19.

One of the studies done on SARS-COV-1 strongly suggested that using ribavirin as therapy
should be reconsidered until further animal studies clarify the effects of ribavirin on
cytokine and chemokine profiles during infection and until ribavirin can be demonstrated to
have a significant effect on reducing viral replication in vivo. Data from a molecular
docking experiment using the SARS-CoV-2 RNA dependent RNA polymerase (RdRp) model identified
the tight binding of sofosbuvir and ribavirin to the coronavirus RdRp, thereby suggesting
possible efficacy of sofosbuvir and ribavirin in treating the COVID-19 infection.

A three-dimensional model of the SARS-CoV-2 (aka 2019-nCoV) 3C-like protease (3CL ) was
prepared then performed virtual screening for purchasable drugs checking the actions,
targets, and side effects of the 16 candidates. Velpatasvir and ledipasvir are examples of
these drugs ( which are inhibitors of the NS5A protein of the hepatitis C virus (HCV). Both
are marketed as approved drugs in combination with sofosbuvir, which is a prodrug nucleotide
analog inhibitor of RNA-dependent RNA polymerase (RdRp, or NS5B).

Interestingly, sofosbuvir has recently been proposed as an antiviral for the SARS-CoV-2 based
on the similarity between the replication mechanisms of the HCV and the coronaviruses.

Based on this data it was suggested that these dual-component HCV drugs, Epclusa
(velpatasvir/sofosbuvir) and Harvoni (ledipasvir/sofosbuvir), may be attractive candidates to
repurpose because they may inhibit two coronaviral enzymes. A drug that can target two viral
proteins substantially reduces the ability of the virus to develop resistance. These
direct-acting antiviral drugs are also associated with very minimal side effects and are
conveniently orally administered.

The aim of this study is to assess the safety and efficacy of the addition of HCV treatment
to the standard regimen for the treatment of COVID-19 patients according to MOHP protocol .