A Clinically Validated, Broadly Active, Oral Viral Superinfection Therapy Could Mitigate Symptoms in Early-stage COVID-19 Patients

Tibor Bakacs; Volker Sandig; Shimon Slavin; Serhat Gumrukcu; David Hardy; Wolfgang Renz; Imre Kovesdi

doi:10.2174/1871526522666220419130403

A Clinically Validated, Broadly Active, Oral Viral Superinfection Therapy Could Mitigate Symptoms in Early-stage COVID-19 Patients

Infect Disord Drug Targets. 2022;22(7):1-6. doi: 10.2174/1871526522666220419130403.

Authors

Tibor Bakacs¹, Volker Sandig², Shimon Slavin³, Serhat Gumrukcu⁴, David Hardy⁵, Wolfgang Renz^{6

7}, Imre Kovesdi⁸

Affiliations

¹ HepC, Inc, 1012 Budapest, Miko str. 3. II. fl. 11., Hungary.
² ProBioGen AG, Standort HBS Herbert-Bayer-Straße 8, 13086 Berlin, Germany.
³ Biotherapy International, The Center for Innovative Cancer Immunotherapy & Cellular Medicine, Tel Aviv, Israel, Weizmann Center, 14 Weizmann Street Floor 15, Suite 1503 Tel Aviv 64239, Israel.
⁴ Seraph Research Institute, 2080 Century Park East, Suite 710, Los Angeles, CA 90067, USA.
⁵ Division of Infectious Diseases, Keck School of Medicine of The University of Southern California (USC), California, USA.
⁶ Division of General Surgery, McGill University, Montreal, Canada.
⁷ Executive School of Management, Technology and Law, University of Sankt Gallen, Sankt Gallen, Switzerland.
⁸ DNAtrix Inc, 10355 Science Center Drive, Suite 110, San Diego, CA 92121, USA.

PMID: 35440336
DOI: 10.2174/1871526522666220419130403

Abstract

More than 200 viruses infect humans, but treatments are available for less than ten of them. To narrow the gap between 'bugs and drugs,' a paradigm shift is required. The "one drug, one bug" approach can be expanded to a "one drug, multiple bugs" strategy such that the host's defense system is targeted rather than the virus. Viral superinfection therapy (SIT) activates interferon genes' natural, antiviral defense system of host cells following exposure to viral infection, e.g., superinfection with an attenuated infectious bursal disease virus (IBDV) with the release of its double-stranded RNA (dsRNA) cargo inside host cells. An attenuated IBDV therapeutic vaccine has successfully treated hepatitis A virus infection (HAV) in marmoset monkeys as well as acute hepatitis B and hepatitis C virus infections (HBV/HCV) in 42 patients. SIT has also been shown to be safe and effective in four patients with chronic HBV or HCV infection with hepatic decompensation. The proof-of-principle of SIT has also been demonstrated in a 43-year-old male patient with COVID-19. Three doses of orally administered IBDV (3x10⁶ IU) alleviated most of his COVID-19 symptoms; even his sense of smell returned within a week. Two additional COVID-19 patients responded similarly to oral treatment with IBDV. Furthermore, a severe herpes zoster ophthalmicus outbreak with orbital edema responded to a combination of acyclovir and 7 doses of IBDV (7x10⁶ IU) within a few days. IBDV is simple to manufacture and affordable, even in resource-limited settings. Acid-resistant IBDV can be orally administered in an outpatient setting, providing simple dosing and high medication adherence. Under an Emergency Use Authorization, the broad-spectrum IBDV drug candidate could be tested immediately in clinical trials and rapidly distributed to millions of early-stage patients with COVID-19. The German Paul Ehrlich Institute is currently supporting a phase I safety study for persons acutely infected with SARS‑CoV-2. An expert team of the US National Institutes of Health-sponsored ACTIV public-private partnership came to the conclusion that the IBDV drug candidate shows merit as a potential treatment for COVID19, and an FDA-approved clinical trial is in the pipelines in Los Angeles.

Keywords: COVID-19; Coronavirus; IBDV; IFN; NIH-ACTIV; R903/78; SARS-CoV-2; SIT; infectious bursal disease virus; interferon; oral treatment; safety; superinfection therapy.