LL-37 for COVID-19

AbstractRecombinant LL‐37 Lactococcus lactis (Oral LL‐37) was designed to prevent progression of COVID‐19 by targeting virus envelope, however, effectiveness and safety of Oral LL‐37 in clinical application was unclear. A total of 238 adult inpatients, open‐labelled, randomized, placebo‐controlled, single‐center study was conducted to investigate the primary end points, including negative conversion time (NCT) of SARS‐CoV‐2 RNA and adverse events (AEs). As early as intervened on 6th day of case confirmed, Oral LL‐37 could significantly shorten NCT (LL‐37 9.80 ± 2.67 vs. placebo 14.04 ± 5.89, p < 0.01). For Oral LL‐37, as early as treated in 6 days, the adjusted hazard ratio (HR) for a primary event of nucleic acid negative outcome was 6.27‐fold higher than 7‐day‐later (HR: 6.276, 95% confidence interval [CI]: 3.631–10.848, p < 0.0001), and the adjusted HR of Oral LL‐37 within 6 days is higher than placebo (HR: 2.427 95% CI: 1.239–4.751, p = 0.0097). No severe AEs were observed during hospitalization and follow‐up investigation. This study shows that early intervention of Oral LL‐37 incredibly reduces NCT implying a potential for clearance of Omicron BA.5.1.3 without evident safety concerns.

Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant pneumonia in December 2019, the cumulative number of infected people worldwide has exceeded 670 million, with over 6.8 million deaths. Despite the marketing of multiple series of vaccines and the implementation of strict prevention and control measures in many countries, the spread and prevalence of SARS-CoV-2 have not been completely and effectively controlled. The latest research shows that in addition to angiotensin converting enzyme II (ACE2), dozens of protein molecules, including AXL, can act as host receptors for SARS-CoV-2 infecting human cells, and virus mutation and immune evasion never seem to stop. To sum up, this review summarizes and organizes the latest relevant literature, comprehensively reviews the genome characteristics of SARS-CoV-2 as well as receptor-based pathogenesis (including ACE2 and other new receptors), mutation and immune evasion, vaccine development and other aspects, and proposes a series of prevention and treatment opinions. It is expected to provide a theoretical basis for an in-depth understanding of the pathogenic mechanism of SARS-CoV-2 along with a research basis and new ideas for the diagnosis and classification, of COVID-19-related disease and for drug and vaccine research and development.