An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment

Abstract

The COVID-19 pandemic is one of the greatest threats to human health in the 21 st century with more than 257 million cases and over 5.17 million deaths reported worldwide (as of November 23, 2021. Various agents were initially proclaimed to be effective against SARS-CoV-2, the etiological agent of COVID-19. Hydroxychloroquine, lopinavir/ritonavir, and ribavirin are all examples of therapeutic agents, whose efficacy against COVID-19 was later disproved. Meanwhile, concentrated efforts of researchers and clinicians worldwide have led to the identification of novel therapeutic options to control the disease including PAXLOVID™ (PF-07321332). Although COVID-19 cases are currently treated using a comprehensive approach of anticoagulants, oxygen, and antibiotics, the novel Pfizer agent PAXLOVID™ (PF-07321332), an investigational COVID-19 oral antiviral candidate, significantly reduced hospitalization time and death rates, based on an interim analysis of the phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness. The scheduled interim analysis demonstrated an 89% reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint). However, there still exists a great need for the development of additional treatments, as the recommended therapeutic options are insufficient in many cases. Thus far, mRNA and vector vaccines appear to be the most effective modalities to control the pandemic. In the current review, we provide an update on the progress that has been made since April 2020 in clinical trials concerning the effectiveness of therapies available to combat COVID-19. We focus on currently recommended therapeutic agents, including steroids, various monoclonal antibodies, remdesivir, baricitinib, anticoagulants and PAXLOVID™ summarizing the latest original studies and meta-analyses. Moreover, we aim to discuss other currently and previously studied agents targeting COVID-19 that either show no or only limited therapeutic activity. The results of recent studies report that hydroxychloroquine and convalescent plasma demonstrate no efficacy against SARS-CoV-2 infection. Lastly, we summarize the studies on various drugs with incoherent or insufficient data concerning their effectiveness, such as amantadine, ivermectin, or niclosamide.

COVID-19 Cardiovascular Connection: A Review of Cardiac Manifestations in COVID-19 Infection and Treatment Modalities

“…Tocilizumab is a recombinant IgG monoclonal antibody that binds to the soluble and membrane-bound receptor for IL-6, which inhibits the signaling pathway thereby decreasing the proinflammatory effects associated with IL-6 103 . Tocilizumab has been shown to reduce mortality and the need for mechanical ventilation in COVID-19 patients; however, the statistical significance has varied among trials 104 , 105 . Many adverse effects have been documented including the development of QT interval prolongation 105 , 106 .…”

“…Paxlovid is a combination of a protease inhibitor and HIV-1 and HIV-2 protease inhibitor (ritonavir) 104 . Paxlovid has been given emergency use authorization by the FDA in the treatment of COVID-19 patients with mild to moderate symptoms as an outpatient medication 110 .…”

Repurposing Probenecid to Inhibit SARS-CoV-2, Influenza Virus, and Respiratory Syncytial Virus (RSV) Replication

“…As for CoV2, it is undeniable that therapeutic antiviral drugs are needed, and a safe and effective broad-spectrum antiviral would be an excellent outcome. Recently, EUAs for Paxlovid, molnupiravir, and remdesivir were issued, which should help facilitate antiviral drug therapy for COVID-19 [ 20 , 38 , 39 ]. Paxlovid is a main protease (Mpro) inhibitor that has been shown to reduce hospitalization or death by 89% when administered within 3 days of symptom onset; molnupiravir incorporates the wrong bases into new viral RNA, and has been shown to reduce hospitalization or death by 30% when administered within 5 days of symptom onset, while remdesivir is a nucleotide prodrug of an adenosine analog that has been shown to reduce time to clinical improvement [ 40 ].…”

Reusable Cu2-xS-modified masks with infrared lamp-driven antibacterial and antiviral activity for real-time personal protection

“…Currently, the Coronavirus disease 2019 (COVID-19) pandemic initiated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a myriad of infection cases and deaths across the globe (262 and 5.22 million, by November 30, 2021) [20] , [21] . There are lots of drugs under investigation and some of them have proved to be effective in inhibiting infection of SARS-CoV-2, such as paxlovid and molnupiravir [22] , [23] , [24] . As the first line of defense against infection, the self-protection measures are still of great importance including hand-washing, social isolation, and facemask-wearing.…”