By January of 2023, the COVID-19 pandemic had led to a reported total of 6,700,883 deaths and 662,631,114 cases worldwide. To date, there have been no effective therapies or standardized treatment schemes for this disease; therefore, the search for effective prophylactic and therapeutic strategies is a primary goal that must be addressed. This review aims to provide an analysis of the most efficient and promising therapies and drugs for the prevention and treatment of severe COVID-19, comparing their degree of success, scope, and limitations, with the aim of providing support to health professionals in choosing the best pharmacological approach. An investigation of the most promising and effective treatments against COVID-19 that are currently available was carried out by employing search terms including “Convalescent plasma therapy in COVID-19” or “Viral polymerase inhibitors” and “COVID-19” in the Clinicaltrials.gov and PubMed databases. From the current perspective and with the information available from the various clinical trials assessing the efficacy of different therapeutic options, we conclude that it is necessary to standardize certain variables—such as the viral clearance time, biomarkers associated with severity, hospital stay, requirement of invasive mechanical ventilation, and mortality rate—in order to facilitate verification of the efficacy of such treatments and to better assess the repeatability of the most effective and promising results.

Cervical cancer is the second leading cause of cancer-related death in Mexico, primarily due to persistent infection with high-risk Alpha-papillomavirus genotypes, such as HPV16 and 18. Next-generation sequencing (NGS) has revealed a high prevalence of Beta- and Gamma-HPVs, mainly Beta-2 types 38b, 80, 107, and 122, in cervical cancer samples from Mexico. Our group previously reported that HPVs 38b, 107, and 122 possess transforming properties in primary fibroblasts; however, the oncogenic potential of E6/E7-HPV80 has not yet been elucidated. For this purpose, primary human fibroblasts were transduced with E6/E7-HPV80 (FB-E6/E7-HPV80), and functional assays were conducted to evaluate changes in proliferation, metabolic activity, and cell migration. RNA-seq analysis identified differentially expressed genes (DEGs) and enriched pathways. Fibroblasts transduced with E6/E7-HPV16 (FB-E6/E7-HPV16) or empty vector (FB-pLVX) served as controls. FB-E6/E7-HPV80 extended their lifespan and exhibited increased proliferation, metabolic activity, and migration capacity. RNA-seq analysis identified 196 upregulated DEGs (such as GPAT2, MST1R, ACAN, SLCO4A1, and CHRNA3) and 887 downregulated DEGs (such as KLHDC7B, TRIM58, CST1, FBLL1, INHBE, and TMEM132D) shared between FB-E6/E7-HPV80 and FB-E6/E7-HPV16. Enriched pathways included p53, TNF, IL-17, apoptosis, cell cycle, etc. These findings suggest that E6/E7-HPV80 exhibits transforming capabilities that could play an important role in cervical carcinogenesis.

From the first report in 1891 by Dr. Coley of the effective treatment of tumors in 1000 patients with Streptococcus and the first successful use of bacterial vectors for transferring therapeutic genes in 1980 by Dr. Schnaffer, bactofection has been shown to be a promising strategy in the fields of vaccination, gene therapy, and cancer therapy. This review describes the general theory of bactofection and its advantages, disadvantages, challenges, and expectations, compiling the most notable advances in 14 vaccination studies, 27 cancer therapy studies, and 13 clinical trials. It also describes the current scope of bactofection and promising results. The extensive knowledge of Salmonella biology, as well as the multiple adequacies of the Ty21a vaccination platform, has allowed notable developments worldwide that have mainly been reflected in therapeutic efforts against cancer. In this regard, we strongly recommend the creation of a recombinant Ty21a model that constitutively expresses the GtgE protease from S. typhimurium, allowing this vector to be used in animal trials, thus enhancing the likelihood of favorable results that could quickly transition to clinical trials. From the current perspective, it is necessary to explore a greater diversity of bacterial vectors and find the best combination of implemented attenuations, generating personalized models that guarantee the maximum effectiveness in cancer therapy and vaccination.

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