Efficacy and Safety of Direct Anti HCV Drugs in the Treatment of SARS-COV-2 (COVID-19)
Efficacy and Safety of Direct Anti HCV Drugs in the Treatment of SARS-COV-2 (COVID-19)
COVID 19 which started from a zoonotic transmission related to crowded markets was confirmed
 to have a high potential for transmission to close contacts on 20 January 2020 by the
 National Health Commission of China and it was announced as a pandemic by the WHO on 11 March
 2020.

 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.

 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.

 Aim of our study is to assess the safety and efficacy of of the addition of HCV treatment to
 the standard regimen for the treatment of patients according to MOHP protocol.
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 .
Inclusion Criteria:

 -  All cases positive for COVID-19

 -  Male and non-pregnant female patients,

 -  18 years of age or older,

 -  All moderate and severe caseswith pneuomnia.

 Exclusion Criteria:

 -  Known allergy or hypersensitivity to the used medications

 -  Known severe liver disease

 -  Use of medications that are contraindicated with the trial medications and that could
 not be replaced or stopped during the trial period

 -  Pregnancy or breast-feeding or known active HCV infection, because of concerns about
 the development of resistance

 -  History of bone marrow transplant

 -  Known G6PD deficiency

 -  Chronic hemodialysis or Glomerular Filtration Rate < 20ml/min

 -  Psoriasis

 -  Porphyria

 -  Concomitant use of digitalis, flecainide, amiodarone, procainamide, or propafenone

 -  Known history of long QT syndrome

 -  Current known QTc>500 msec

 -  Pregnant or nursing

 -  Weight < 35kg

 -  Seizure disorder

 -  Patients receiving Amiodarone.