An Insight to Heat Shock Protein 90: A Remedy for Multiple Problems.

Heat shock protein 90 (Hsp90) is a chaperone protein that prevents many other proteins from aggregating by folding them in a certain way. Hsp90 consists of three structural domains: N-terminal, middle and C-terminal domains. Hsp90 has many activities in numerous proteins and signaling pathways like chimeric fusion proteins, steroid hormone receptors, tumor suppressor genes, and cell cycle regulatory proteins. The role of Hsp90 is not only in cancer but also in other diseases like COVID-19, leishmaniasis, diabetes, flavi virus, systemic sclerosis, grass carp reovirus, psoriasis, malaria, cardiac fibrosis, and alcohol-related liver diseases. This review is a compilation of the pharmacological profile of Hsp90 inhibitors, problems associated with them, and suggested remedies for the same.

Neuromodulatory effects of SARS-CoV2 infection: Possible therapeutic targets.

INTRODUCTION: Although SARS-CoV-2 primarily manifests in the form of respiratory symptoms, emerging evidence suggests that the disease is associated with numerous neurological complications, such as stroke and Guillain-Barre syndrome. Hence, further research is necessary to seek possible therapeutic targets in the CNS for effective management of these complications. AREAS COVERED: This review examines the neurological complications associated with SARS-CoV-2 infections and the possible routes of infection. It progresses to illuminate the possible therapeutic targets for effective management of these neuromodulatory effects and the repurposing of drugs that could serve this purpose. To this end, literature from the year 1998-2021 was derived from PubMed. EXPERT OPINION: The neurological manifestations associated with COVID-19 may be related to poor prognosis and higher comorbidity. Identification of the key molecular targets in the brain that are potential indicators of the observed neuropathology, such as inflammatory mediators and chromatin modifiers, is key. The repurposing of existing drugs to target potential candidates could reduce the mortality attributed to these associated neurological complications.

Repurposing approved drugs for cancer therapy.

BACKGROUND: Many drugs approved for other indications can control the growth of tumor cells and limit adverse events (AE). DATA SOURCES: Literature searches with keywords 'repurposing and cancer' books, websites: https://clinicaltrials.gov/, for drug structures: https://pubchem.ncbi.nlm.nih.gov/. AREAS OF AGREEMENT: Introducing approved drugs, such as those developed to treat diabetes (Metformin) or inflammation (Thalidomide), identified to have cytostatic activity, can enhance chemotherapy or even replace more cytotoxic drugs. Also, anti-inflammatory compounds, cytokines and inhibitors of proteolysis can be used to control the side effects of chemo- and immuno-therapies or as second-line treatments for tumors resistant to kinase inhibitors (KI). Drugs specifically developed for cancer therapy, such as interferons (IFN), the tyrosine KI abivertinib TKI (tyrosine kinase inhibitor) and interleukin-6 (IL-6) receptor inhibitors, may help control symptoms of Covid-19. AREAS OF CONTROVERSY: Better knowledge of mechanisms of drug activities is essential for repurposing. Chemotherapies induce ER stress and enhance mutation rates and chromosome alterations, leading to resistance that cannot always be related to mutations in the target gene. Metformin, thalidomide and cytokines (IFN, tumor necrosis factor (TNF), interleukin-2 (IL-2) and others) have pleiomorphic activities, some of which can enhance tumorigenesis. The small and fragile patient pools available for clinical trials can cloud the data on the usefulness of cotreatments. GROWING POINTS: Better understanding of drug metabolism and mechanisms should aid in repurposing drugs for primary, adjuvant and adjunct treatments. AREAS TIMELY FOR DEVELOPING RESEARCH: Optimizing drug combinations, reducing cytotoxicity of chemotherapeutics and controlling associated inflammation.