Beyond Vaccines: Clinical Status of Prospective COVID-19 Therapeutics

Abstract

Since November 2019 the SARS-CoV-2 pandemic has caused nearly 200 million infection and more than 4 million deaths globally (Updated information from the World Health Organization, as on 2nd Aug 2021). Within only one year into the pandemic, several vaccines were designed and reached approval for the immunization of the world population. The remarkable protective effects of the manufactured vaccines are demonstrated in countries with high vaccination rates, such as Israel and UK. However, limited production capacities, poor distribution infrastructures and political hesitations still hamper the availability of vaccines in many countries. In addition, due to the emergency of SARS-CoV-2 variants with immune escape properties towards the vaccines the global numbers of new infections as well as patients developing severe COVID-19, remains high. New studies reported that about 8% of infected individuals develop long term symptoms with strong personal restrictions on private as well as professional level, which contributes to the long socioeconomic problems caused by this pandemic. Until today, emergency use-approved treatment options for COVID-19 are limited to the antiviral Remdesivir, a nucleoside analogue targeting the viral polymerase, the glucocorticosteroide Dexamethasone as well as neutralizing antibodies. The therapeutic benefits of these treatments are under ongoing debate and clinical studies assessing the efficiency of these treatments are still underway. To identify new therapeutic treatments for COVID-19, now and by the post-pandemic era, diverse experimental approaches are under scientific evaluation in companies and scientific research teams all over the world. To accelerate clinical translation of promising candidates, repurposing approaches of known approved drugs are specifically fostered but also novel technologies are being developed and are under investigation. This review summarizes the recent developments from the lab bench as well as the clinical status of emerging therapeutic candidates and discusses possible therapeutic entry points for the treatment strategies with regard to the biology of SARS-CoV-2 and the clinical course of COVID-19.

Identification of Hypericin as a Candidate Repurposed Therapeutic Agent for COVID-19 and Its Potential Anti-SARS-CoV-2 Activity

“…Furthermore, they are targeted to specific clinical stages of the disease or patient groups. In search for more therapeutic options to contain the morbidity and mortality caused by SARS-CoV-2, drugs that target the viral proteins and the host molecules that drive the response against infection are being studied, as combination therapies are a good approach to successfully fight this disease ( Kumar et al, 2021 ). Also, drug repurposing has been highlighted as a relevant strategy to speed up the identification of compounds with anti-SARS-CoV-2 activity and, more importantly, reduce time and cost for clinical implementation of any potential drugs identified in experimental conditions.…”

“…However, their therapeutic benefits are still being fully determined. Additionally, several antiviral drugs have been investigated for the treatment of COVID-19 1 who.int/en/activities/tracking-SARS-CoV-2-variants 2 ema.europa.eu 3 fda.gov in clinical trials, such as Favipiravir, Lopinavir/Ritonavir, Umifenovir (arbidol), and the new drug Paxvolid (Jomah et al, 2020;Kumar et al, 2021;Mahase, 2021). Furthermore, host directed therapies, aiming to impair virus-host specific interface mechanisms, and immunomodulators that would counteract the exacerbated immune response associated with the disease severity are other relevant therapeutic options under investigation (Kumar et al, 2021).…”

“…Presently, the process of vaccination against SARS-CoV-2 is ongoing worldwide with distinct types of immunogens, including inactivated virus, adenoviral vectors, and viral RNA, among others ( Abdulla et al, 2021 ; Kumar et al, 2021 ). Vaccines constitute one of the most important public health strategies to reduce disease burden.…”

Repurposing Antifungals for Host-Directed Antiviral Therapy?

“…The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting coronavirus disease 2019 (COVID- 19) have impressively shown how quickly the spread of a novel virus becomes a major threat for public health worldwide [1]. The ongoing pandemic with high mortality and morbidity rates highlights the urgent need for safe and fast development of new pharmaceutics to combat newly emerging viral infections [2,3]. While the ultrafast development of vaccines to fight SARS-CoV-2 has been an unprecedented success story, the high mutation rates leading to rapidly changing viral genomes also require a continuous update of vaccines [4][5][6].…”

Perceptions towards COVID-19 Vaccines and Willingness to Vaccinate in Nepal

“…As of late October 2021, there are more than 243 million cases of infections and 4.9 million deaths worldwide [1]. Except for Remdesivir, no other treatment options have been approved against the disease yet, and hence the global community is highly reliant on preventive measures to contain the catastrophe [2]. Vaccines are one of the most effective preventive measures to limit the spread of the disease, and there has been tremendous, accelerated success in the field of COVID-19 vaccine research and development [3].…”