A Systematic Review of the Global Intervention for SARS-CoV-2 Combating: From Drugs Repurposing to Molnupiravir Approval

Abstract

The rising outbreak of SARS-CoV-2 continues to unfold all over the world. The development of novel effective antiviral drugs to fight against SARS-CoV-2 is a time cost. As a result, some specific FDA-approved drugs have already been repurposed and authorized for COVID-19 treatment. The repurposed drugs used were either antiviral or non-antiviral drugs. Accordingly, the present review thoroughly focuses on the repurposing efficacy of these drugs including clinical trials experienced, the combination therapies used, the novel methods followed for treatment, and their future perspective. Therefore, drug repurposing was regarded as an effective avenue for COVID-19 treatment. Recently, molnupiravir is a prodrug antiviral medication that was approved in the United Kingdom in November 2021 for the treatment of COVID-19. On the other hand, PF-07321332 is an oral antiviral drug developed by Pfizer. For the treatment of COVID-19, the PF-07321332/ritonavir combination medication is used in Phase III studies and was marketed as Paxlovid. Herein, we represented the almost history of combating COVID-19 from repurposing to the recently available oral anti-SARS-CoV-2 candidates, as a new hope to end the current pandemic.

Investigating the possible mechanisms of pirfenidone to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and/or anti-SARS-CoV-2

“…Coronavirus illness (COVID-19) is a global pandemic that has caused problems for public health and the economy [132] , [133] , [134] , [135] . In patients with COVID-19, cytokine storms, multiorgan failure, and especially acute respiratory distress syndrome (ARDS) are the major causes of mortality and morbidity [136] , [137] , [138] . The majority of COVID-19 sufferers die from a fulminant ARDS [139] , [140] , [141] .…”

Ligand-based design, synthesis, computational insights, andin vitrostudies of novelN-(5-Nitrothiazol-2-yl)-carboxamido derivatives as potent inhibitors of SARS-CoV-2 main protease

“…Lately, a new synthetic nucleoside derivative prodrug, named molnupiravir, was approved in the U.K for COVID-19 treatment. Molnupiravir acts by copying errors during RNA virus replication 26 . It is an active orally RdRp inhibitor with reasonable pharmacokinetic features.…”

“…Additionally, the oral antiviral drug, named PF-07321332, was developed by Pfizer For COVID-19 treatment as well. PF-07321332 acts as an active Mpro inhibitor of the virus 26 . Protease inhibitors act by interrupting the protease enzyme cutting, thus, the polypeptide processing to smaller protein is blocked.…”

“…PF-07321332 is co-administered with ritonavir in low doses as a booster to enhance the PF-07321332 bloodstream levels 28 . The combination of ritonavir/PF-07321332 was marketed as paxlovid 26 .…”

Recent advances in small-molecular therapeutics for COVID-19

“…There are already reviews that describe the small molecules against SARS-CoV-2, especially the drug repurposing strategies. 4–7 We here comprehensively summarize the current advances and challenges in small-molecular therapeutics based on almost all potential targets against SARS-CoV-2, including virus-targeted and host-targeted inhibitors, as well as immune response modulators and high-throughput drug repurposing.…”