MIR 19 for COVID-19

Abstract The ability of small nucleic acids to modulate gene expression via a range of processes has been widely explored. Compared with conventional treatments, small nucleic acid therapeutics have the potential to achieve long-lasting or even curative effects via gene editing. As a result of recent technological advances, efficient small nucleic acid delivery for therapeutic and biomedical applications has been achieved, accelerating their clinical translation. Here, we review the increasing number of small nucleic acid therapeutic classes and the most common chemical modifications and delivery platforms. We also discuss the key advances in the design, development and therapeutic application of each delivery platform. Furthermore, this review presents comprehensive profiles of currently approved small nucleic acid drugs, including 11 antisense oligonucleotides (ASOs), 2 aptamers and 6 siRNA drugs, summarizing their modifications, disease-specific mechanisms of action and delivery strategies. Other candidates whose clinical trial status has been recorded and updated are also discussed. We also consider strategic issues such as important safety considerations, novel vectors and hurdles for translating academic breakthroughs to the clinic. Small nucleic acid therapeutics have produced favorable results in clinical trials and have the potential to address previously “undruggable” targets, suggesting that they could be useful for guiding the development of additional clinical candidates.

Since the beginning of the COVID-19 pandemic, the scientific community has focused on prophylactic vaccine development. In parallel, the experience of the pharmacotherapy of this disease has increased. Due to the declining protective capacity of vaccines against new strains, as well as increased knowledge about the structure and biology of the pathogen, control of the disease has shifted to the focus of antiviral drug development over the past year. Clinical data on safety and efficacy of antivirals acting at various stages of the virus life cycle has been published. In this review, we summarize mechanisms and clinical efficacy of antiviral therapy of COVID-19 with drugs based on plasma of convalescents, monoclonal antibodies, interferons, fusion inhibitors, nucleoside analogs, and protease inhibitors. The current status of the drugs described is also summarized in relation to the official clinical guidelines for the treatment of COVID-19. In addition, here we describe innovative drugs whose antiviral effect is provided by antisense oligonucleotides targeting the SARS-CoV-2 genome. Analysis of laboratory and clinical data suggests that current antivirals successfully combat broad spectra of emerging strains of SARS-CoV-2 providing reliable defense against COVID-19.