Cephalexin for COVID-19

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) caused an outbreak in 2002-2003, spreading to 29 countries with a mortality rate of about 10%. Strict quarantine and infection control methods quickly stopped the spread of the disease. Later research showed that SARS-CoV came from animals (zoonosis) and stressed the possibility of a similar spread from host to human, which was clearly shown by the COVID-19 outbreak. The COVID-19 pandemic, instigated by SARS-CoV-2, has affected 776 million confirmed cases and more than seven million deaths globally as of Sept 15, 2024. The existence of animal reservoirs of coronaviruses continues to pose a risk of re-emergence with improved fitness and virulence. Given the high death rate (up to 70 percent) and the high rate of severe sickness (up to 68.7 percent in long-COVID patients), it is even more critical to identify new therapies as soon as possible. This study combines research on antivirals that target SARS coronaviruses that have been conducted over the course of more than twenty years. It is a beneficial resource that might be useful in directing future studies.

(1) Background: Drug repositioning is an unconventional drug discovery approach to explore new therapeutic benefits of existing drugs. Currently, it emerges as a rapid avenue to alleviate the COVID-19 pandemic disease. (2) Methods: Herein, we tested the antiviral activity of anti-microbial and anti-inflammatory Food and Drug Administration (FDA)-approved drugs, commonly prescribed to relieve respiratory symptoms, against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the viral causative agent of the COVID-19 pandemic. (3) Results: Of these FDA-approved antimicrobial drugs, Azithromycin, Niclosamide, and Nitazoxanide showed a promising ability to hinder the replication of a SARS-CoV-2 isolate, with IC50 of 0.32, 0.16, and 1.29 µM, respectively. We provided evidence that several antihistamine and anti-inflammatory drugs could partially reduce SARS-CoV-2 replication in vitro. Furthermore, this study showed that Azithromycin can selectively impair SARS-CoV-2 replication, but not the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). A virtual screening study illustrated that Azithromycin, Niclosamide, and Nitazoxanide bind to the main protease of SARS-CoV-2 (Protein data bank (PDB) ID: 6lu7) in binding mode similar to the reported co-crystalized ligand. Also, Niclosamide displayed hydrogen bond (HB) interaction with the key peptide moiety GLN: 493A of the spike glycoprotein active site. (4) Conclusions: The results suggest that Piroxicam should be prescribed in combination with Azithromycin for COVID-19 patients.