Minocycline for COVID-19

Introduction: Minocycline a semi-synthetic tetracycline is a potential therapeutic option for COVID-19 because of its anti-inflammatory and immunomodulatory effects. Moreover, its antioxidant, antiviral, and antiapoptotic effects have been proven. In this study, the efficacy of minocycline in the therapy of COVID-19 patients has been evaluated. Methods: A randomized double-blind placebo-controlled clinical trial was performed in Mashhad, Iran. 40 outpatients were randomized to either the treatment with the minocycline group or the placebo group, in a 1:1 ratio with 20 patients in each group. The Iranian National COVID-19 Therapy Regimen at the time was used in both groups and patients in the treatment group also received oral minocycline 100 mg twice day for 14 days. Patients in both groups were followed on days 3, 7, and 14 after initiating therapy for clinical symptom improvement, improvement of lymphocytes, leukocytes, C-reactive protein (CRP) and SpO2. Results: A total of 40 patients with similar demographic and disease characteristics were enrolled. Results showed that the time interval until clinical symptoms improvement was significantly reduced in the minocycline group (6.85±0.79, day) compared to the placebo (10.95±1.18, day) group (P=0.006). Moreover, the time interval until leukocytes reaching normal limits was significantly reduced in the minocycline group (3.95±0.59, day) compared to the placebo (6.72±1.25, day) group (P=0.046). Conclusion: In this randomized double-blind placebo-controlled study, minocycline (100 mg, BID for 14 days) reduced the duration of clinical symptoms improvement as well as the duration of white blood cell (WBC) normalizing in outpatients of COVID-19 disease.

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.

Coronavirus disease 2019 (COVID-19) remains a global threat to human health because of its sporadic prevalence despite the development of COVID-19 vaccines and several drugs such as remdesivir and molnupiravir. Moreover, long COVID has become another global issue. No standard treatment has been established for long COVID. Therefore, finding quickly effective and low-priced drugs against COVID-19 and long COVID-19 and conducting clinical trials on these drugs remains crucial for global health. Drug repurposing is a well-known strategy for redeploying existing licensed drugs for newer indications, enabling the shortest possible transition from bench to bed side. Regarding existing licensed drugs for COVID-19, tetracycline has been administered since the beginning of 2020 due to its efficacy in inhibiting COVID-19 and its anti-inflammatory effects. Neuroinflammation associated with microglia in the central nervous system is considered one of the pathophysiologies of long COVID. Further, tetracycline is expected to be efficacious against long COVID because it inhibits microglial activity. Recently, minocycline has been efficacious against long COVID. Considering other existing licensed drugs for COVID-19, Kampo medicine, which is a traditional Japanese medicine, has been prescribed during the COVID-19 pandemic due to its efficacy in inhibiting severe acute respiratory syndrome corona virus 2 and its anti-inflammatory effects. Recently, Kampo medicine has been effective for long COVID. Multidrug treatment is effective because of the synergistic effects associated with the different mechanisms of action of the concerned drugs. Therefore, a combination of minocycline and Kampo medicine may be more efficacious against COVID-19 and long COVID.

IntroductionThe COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. MethodsExtensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors.ResultsResults revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. DiscussionThe key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies.