Severe acute respiratory syndrome coronavirus-2 (SARS‐CoV‐2) or Coronavirus disease of 2019 (COVID-19) is a novel coronavirus that belongs to the same family of SARS‐CoV as Middle East respiratory syndrome coronavirus (MERS‐CoV) [1]. SARS‐CoV‐2 mainly infects the respiratory system and is transmitted via respiratory droplets through close contact [2]. In early January 2020, it was identified as the cause of an epidemic of pneumonia in the Chinese city of Wuhan, which led to a subsequent global pandemic.[2]

To date, there is no specific effective antiviral treatment for COVID-19. In most cases, the disease has a mild or moderate course, although up to 5%–10% of the patients develop a severe, potentially life-threatening disease. A global effort is being made to find an effective treatment against COVID-19. These efforts include trying lopinavir (LPV)/ritonavir (RTV), interferon (IFN) β-1a, hydroxychloroquine/chloroquine [3], and ivermectin [4], which have not proven to be successful.

Coronaviruses are large, positive-sense RNA viruses, including alpha, beta, delta, and gamma genera [5]. The coronavirus replication machinery is a large multi-subunit complex [6]. The most highly conserved protein in all known RNA viruses is the viral monomeric RNA-dependent RNA-polymerase (RdRp). The[6]re are now several drugs, such as favipiravir (FVP) [7] and remdesivir [8], which bind to the RdRp active site and have been approved to treat other RNA viral diseases.

The available data about SARS-CoV-2 shows a viral genome replication similar to that of the hepatitis C virus (HCV) [9]. The virus enters the cell by endocytosis, is uncoated, and open reading frames 1a and 1b (ORF1a and ORF1b) of the positive-strand RNA is translated to produce nonstructural proteins, including cysteine and serine proteases, helicase, and RdRp. Recent data suggest that HCV direct-acting antiviral drugs (DAAs), which are used in HCV management, might be effective against the SARS-CoV-2 virus through RdRp targeting [10], [11].

Sofosbuvir is a HCV-DAA with NS5B RdRp inhibitory activity. It has been used in combination with several NS5A protein inhibitors, such as daclatasvir or ledipasvir, with high efficacy for HCV treatment [12]. The introduction of DAAs was considered a milestone in HCV eradication in Egypt, with a sustained virological response rate of almost 100%, using certain DAA combinations [13].

Molecular docking was performed to test several HCV-DAAs, including sofosbuvir, against SARS-CoV-2 RdRp, and the results were promising. Therefore, DAAs might have inhibitory activity against the newly emerged coronavirus [14].

Nitazoxanide, a drug developed initially as an antiprotozoal agent, has a broad-spectrum antiviral activity and can inhibit the replication of a wide range of RNA and DNA viruses in cell-culture assays. It exhibits in vitro activity against MERS-CoV and several coronaviruses [15]. In humans, a Phase IIb/III clinical trial found that oral administration of nitazoxanide reduced the duration of clinical symptoms and viral shedding compared to placebo in individuals with influenza [16].

Currently, sufficient data are not available on the efficacy of DAAs or nitazoxanide in treating patients with COVID-19 infection. Therefore, we aimed to evaluate the efficacy and safety of sofosbuvir/ledipasvir and nitazoxanide to treat COVID-19 infection. Both drugs are inexpensive and available throughout the world.