The need for a multi-level drug targeting strategy to curb the COVID-19 pandemic

Abstract

Introduction 3. The effects of vaccines on the COVID-19 pandemic 4. Drug based concepts for the prevention of COVID-19 4.1 Factors contributing to variable susceptibility to SARS-CoV-2 infection 4.2 Drug based examples of prevention targets against COVID-19 infection 5. Drug targeting based theory and methods against SARS-CoV-2 6. Examples of drugs that are widely used in COVID-19 patients 7. Examples of drugs that could be used in COVID-19 8. Pharmacological and toxicological aspects of drugs against COVID-19 9. New developments affecting multi-level drug targeting strategies against COVID-19 10. Conclusions 11. Author contributions 12. Ethics approval and consent to participate 13. Acknowledgment 14. Funding 15. Conflict of interest 16. References Abbreviations: ACE2, angiotensin converting enzyme 2; ARDS, acute respiratory distress syndrome; EMA, European medicines agency; FDA, food and drug admin-istration; FIASMA, inhibitors of acid sphingomyelinase; GM-CSF, granulocyte-macrophage colony-stimulating fac-tor; COVID-19, coronavirus disease 2019; IL, interleukin, e.g., IL-1, IL-6, IL-8; iv, intravenous; IND, investigational new drugs; LDH, lactate dehydrogenase; LMWH, low molecular weight heparin; MERS-CoV, Middle East Respiratory Syndrome coronavirus; p.o., oral administration; QALY, quality-adjusted life years; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; sc, sub-cutaneous; TMPRSS2, transmembrane protease serine 2; WHO, world health organization.

Omicron Genetic and Clinical Peculiarities That May Overturn SARS-CoV-2 Pandemic: A Literature Review

“…Regulatory authorities are continuously evaluating already approved drugs, and hundreds of medicines with newly identified targets have been proposed [64]. The effect of approved drugs and those under investigation against the Omicron variant remains to be further investigated.…”

“…Molnupiravir is orally available and, when administered early in non-hospitalised, unvaccinated adults with mild to moderate COVID-19, it reduces the overall hospitalisation and death risk by approximately 31% [70]. No data on the Omicron variant are yet available, but molnupiravir is expected to retain activity against all SARS-CoV-2 VOCs [64].…”

“…The main problem is linked to ritonavir, a potent cytochrome and P-glycoprotein inhibitor, raising concerns about drug-drug interactions. The combination is expected to retain activity against all the SARS-CoV-2 variants, including the new Omicron [64].…”

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Management of Mild-to-Moderate Symptomatic COVID-19

“…It would certainly be useful to carry out robust prospective randomized studies to confirm the results of our preliminary research, carried out with a retrospective observational design [ 6 ]. The importance of identifying drug combinations for multiple targets, addressing different stages of COVID-19 and different pathophysiological changes, has also been emphasized by others [ 165 ]. This approach envisages that, from an experimental point of view, multicenter studies can be initiated on large numbers of patients treated with different combinations of drugs and supplements, but following a common protocol of recruitment, data collection, and analysis, to compare the different options in the field by means of multivariate analysis.…”

Questioning Established Theories and Treatment Methods Related to Iron and Other Metal Metabolic Changes, Affecting All Major Diseases and Billions of Patients

“…However, the use of luspatercept in thalassaemia major is questionable since, even if haematopoiesis can be increased in patients, this can only produce abnormal, non-functional haemoglobin. Similarly, serious concerns remain in other aspects of therapy, such as the safety, efficacy and the cost of luspatercept and also of other biologics, including those used in the treatment of COVID-19, since, in general, the immunogenicity and other toxic side effects of these compounds have not yet been fully investigated [90,91].…”