Potential Prophylactic Treatments for COVID-19

Abstract

The World Health Organization declared the SARS-CoV-2 outbreak a Public Health Emergency of International Concern at the end of January 2020 and a pandemic two months later. The virus primarily spreads between humans via respiratory droplets, and is the causative agent of Coronavirus Disease 2019 (COVID-19), which can vary in severity, from asymptomatic or mild disease (the vast majority of the cases) to respiratory failure, multi-organ failure, and death. Recently, several vaccines were approved for emergency use against SARS-CoV-2. However, their worldwide availability is acutely limited, and therefore, SARS-CoV-2 is still expected to cause significant morbidity and mortality in the upcoming year. Hence, additional countermeasures are needed, particularly pharmaceutical drugs that are widely accessible, safe, scalable, and affordable. In this comprehensive review, we target the prophylactic arena, focusing on small-molecule candidates. In order to consolidate a potential list of such medications, which were categorized as either antivirals, repurposed drugs, or miscellaneous, a thorough screening for relevant clinical trials was conducted. A brief molecular and/or clinical background is provided for each potential drug, rationalizing its prophylactic use as an antiviral or inflammatory modulator. Drug safety profiles are discussed, and current medical indications and research status regarding their relevance to COVID-19 are shortly reviewed. In the near future, a significant body of information regarding the effectiveness of drugs being clinically studied for COVID-19 is expected to accumulate, in addition to information regarding the efficacy of prophylactic treatments.

Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike–ACE2 Interaction

“…We speculate that significant therapeutic benefits might be gained in combination with antiviral drugs with complementary mechanisms of action such as Paxlovid (nirmatrelvir/ritonavir) and molnupiravir. Prophylactic treatments are also of potential high value for COVID19 . Although oral availability of pixatimod is poor, we also suggest that direct intranasal delivery of pixatimod as a pre-exposure prophylactic strategy would be worth investigation, in view of recent positive data on the delivery of nebulized heparin for treatment of ARDS, and also COVID-19 treatment …”

Preclinical Evaluation of Chicken Egg Yolk Antibody (IgY) Anti-RBD Spike SARS-CoV-2—A Candidate for Passive Immunization against COVID-19

“…The main clinical signs of COVID-19 infection are fever, cough, pharyngitis, sore throat, dyspnea, fatigue, congestion and runny nose, asthenia and myalgia, nausea and vomiting, and diarrhea [5,6]. At present, a number of prophylactic and therapeutic treatments are being developed and repurposed for COVID-19, including passive immunization, viral drugs, and vaccines [7][8][9].…”

DNA aptamers masking angiotensin converting enzyme 2 as an innovative way to treat SARS-CoV-2 pandemic

“…The recent observation that in M. musculus, the ACE2 K353H substitution protects the species from the SARS-CoV-2 infection further highlights the critical role played by this residue in the virus life cycle [12] . Since the beginning of the pandemic, several treatments have been proposed to limit worsening of symptoms due to cytokine storm and to prevent hospitalization, including the repurposing of existing drugs [13] , [14] , [15] , [16] , natural products and herbal medicines [17] or a combination of both [18] , some of which successfully reduced hospitalization or favored recovery from the disease [15] , [19] . Recently developed vaccines [20] and neutralizing monoclonal antibodies [21] , [22] have demonstrated particular efficacy in prevention and progression of severe COVID-19 [23] , [24] , decreasing hospitalization and intensive care unit (ICU) admissions [25] , although it is conceivable that the treatment tools targeting viral S1 might be less efficient in hampering the spread of different SARS-CoV-2 variants in the worldwide population [26] which displayed higher probability of infectivity [27] and mortality [28] , [29] than the original Wuhan strain [30] .…”