Races of small molecule clinical trials for the treatment of COVID‐19: An up‐to‐date comprehensive review

Abstract

The coronavirus disease‐19 (COVID‐19) pandemic has become a global threat since its first outbreak at the end of 2019. Several review articles have been published recently, focusing on the aspects of target biology, drug repurposing, and mechanisms of action (MOAs) for potential treatment. This review gathers all small molecules currently in active clinical trials, categorizes them into six sub‐classes, and summarizes their clinical progress. The aim is to provide the researchers from both pharmaceutical industries and academic institutes with the handful information and dataset to accelerate their research programs in searching effective small molecule therapy for treatment of COVID‐19.

Paxlovid: Mechanism of Action, Synthesis, and In Silico Study

“…A similar decrease was observed in patients treated within five days of the onset of symptoms, with 1% (6.607) in the nirmatrelvir group by day 28 (without death) and 6.7% (41.612) in the placebo group (10 deaths). In general, by day 28, no casualties were informed among patients receiving nirmatrelvir, while 10 (1.6%) in the placebo group lost their lives ( Figure 5 ) [ 25 , 30 , 47 , 48 ]. In another study, high confidence was obtained in the selection of the 300 mg nirmatrelvir diet in combination with the 100 mg ritonavir as BID over a 5-day term for phase 2/3 clinical trials in patients with COVID-19 [ 49 ].…”

Use of Antiviral Agents and other Therapies for COVID-19

“…Several comprehensive reviews on the topic have been published. [69][70][71] Many of these drugs are now in the late stages of clinical testing (phase III/IV), 72 though the majority of these continue to be repurposed drugs already approved for other indications, including those discussed earlier. 73 As these small molecule drugs are structurally diverse, they are best categorized by their proposed target or mode of action as follows: (1) those blocking virus-cell binding and cell entry; (2) those inhibiting virus replication; (3) drugs targeting cytokine storm syndrome (CSS); and (4) other less common treatment types (i.e., the use of anticoagulants and antioxidants).…”

Are we ready to combat the ecotoxicity of COVID-19 pharmaceuticals? An in silico aquatic risk assessment

“…Additionally, the work aims to promote the use of ATS in the ecotoxicity assessment of pharmaceuticals as major environment contaminants. For the present study, we have compiled a list of 85 pharmaceuticals (77 repurposed approved drug molecules, 1 approved drug for emergency use by US-FDA and 3 molecules under trials, and 4 control molecules to compare the ecotoxicity threshold) from the literature and web platforms ( Ojha et al., 2021 ; Hu et al., 2021 ; Two COVID-19 antiviral pills advance to late-stage trials 2023 ; DrugBank online 2023 ; Tarighi et al., 2021 ; Pfizer Announces Submission of New Drug Application to the U.S. FDA for PAXLOVID™, 2023 ) ensuring the inclusion of maximum drug candidates employed directly or indirectly in the treatment of COVID-19 disease (the detailed list of studied pharmaceuticals with their therapeutics class, SMILES, InChI, IUPAC names, MW and MLOGP is given in Table S1 in Supplementary Materials). Out of four molceules under clinical trials, nirmatrelvir [PF-07321332] authorized for emergency use in both high-risk adults and high-risk pediatric patients 12 years of age and older weighing at least 40 kg in combination with ritonavir tablets using brand name of PAXLOVID™ ( Pfizer Announces Submission of New Drug Application to the U.S. FDA for PAXLOVID™ 2023 ).…”