COVID-19 update: The race to therapeutic development

Abstract

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents an unprecedented challenge to global public health. At the time of this review, COVID-19 has been diagnosed in over 40 million cases and associated with 1.1 million deaths worldwide. Current management strategies for COVID-19 are largely supportive, and while there are more than 2000 interventional clinical trials registered with the U.S. National Library of Medicine (clinicaltrials.gov), results that can clarify benefits and risks of candidate therapies are only gradually becoming available. We herein describe recent advances in understanding SARS-COV-2 pathobiology and potential therapeutic targets that are involved in viral entry into host cells, viral spread in the body, and the subsequent COVID-19 progression. We highlight two major lines of therapeutic strategies for COVID-19 treatment: 1) repurposing the existing drugs for use in COVID-19 patients, such as antiviral medications (e.g., remdesivir) and immunomodulators (e.g., dexamethasone) which were previously approved for other disease conditions, and 2) novel biological products that are designed to target specific molecules that are involved in SARS-COV-2 viral entry, including neutralizing antibodies against the spike protein of SARS-COV-2, such as REGN-COV2 (an antibody cocktail) and LY-COV555, as well as recombinant human soluble ACE2 protein to counteract SARS-COV-2 binding to the transmembrane ACE2 receptor in target cells. Finally, we discuss potential drug resistance mechanisms and provide thoughts regarding clinical trial design to address the diversity in COVID-19 clinical manifestation. Of note, preventive vaccines, cell and gene therapies are not within the scope of the current review.

Nucleoside Analogs and Nucleoside Precursors as Drugs in the Fight against SARS-CoV-2 and Other Coronaviruses

“…Presently, SARS-CoV-2 infection therapy includes immunomodulatory drugs, plasma from individuals recovered from COVID-19, and several pharmacological treatments [ 81 ]. In this regard, despite numerous repurposed drugs being tested, only the nucleoside analog remdesivir has been officially approved by the American Food and Drug Administration (FDA) agency to date [ 82 ].…”

Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2

“…Effective pharmacological interventions are therefore urgently needed. Since the first report of COVID-19 in late 2019, relevant progress has been achieved in drug discovery and development within a remarkable timeline [ [7] , [8] , [9] , [10] , [11] ]. Several vaccines and drugs are undergoing clinical trials, but research on novel antivirals remains important.…”

Warnings regarding the potential coronavirus disease 2019 (COVID-19) transmission risk: Vaccination is not enough

“…Caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), Coronavirus Disease 2019 (COVID-19) pandemic has continued to spread around the world and led to a global health emergency of inconceivable magnitude. 1,2 Currently, vaccines, including Pfizer-BioNTech COVID-19 vaccine and Moderna's COVID-19 vaccine, are authorized for emergency use to prevent COVID-19. 3 Previous study indicated that use of a vaccine in combination with measures which could reduce contact between susceptible individuals and COVID-19 carriers will significantly decrease the per-day risk of infection so long as at least 50% of people receive it.…”