Quinine for COVID-19

While vaccination campaigns are ongoing worldwide, there is still a tremendous medical need for efficient antivirals against SARS-CoV-2 infection. Among several drug candidates, chloroquine (CQN) and hydroxychloroquine (H-CQN) were tested intensively, and any contentious therapeutic effect of both has been discussed controversially in the light of severe side effects and missing efficacy. Originally, H-CQN descended from the natural substance quinine, a medicinal product used since the Middle Ages, which actually is regulatory approved for various indications. We hypothesized that quinine also exerts anti-SARS-CoV-2 activity. In Vero cells, quinine inhibited SARS-CoV-2 infection more effectively than CQN, and H-CQN and was less toxic. In human Caco-2 colon epithelial cells as well as the lung cell line A549 stably expressing ACE2 and TMPRSS2, quinine also showed antiviral activity. In consistence with Vero cells, quinine was less toxic in A549 as compared to CQN and H-CQN. Finally, we confirmed our findings in Calu-3 lung cells, expressing ACE2 and TMPRSS2 endogenously. In Calu-3, infections with high titers of SARS-CoV-2 were completely blocked by quinine, CQN, and H-CQN in concentrations above 50 µM. The estimated IC50s were ~25 µM in Calu-3, while overall, the inhibitors exhibit IC50 values between ~3.7 to ~50 µM, dependent on the cell line and multiplicity of infection (MOI). Conclusively, our data indicate that quinine could have the potential of a treatment option for SARS-CoV-2, as the toxicological and pharmacological profile seems more favorable when compared to its progeny drugs H-CQN or CQN.

Background The global pandemics of severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID-19 have caused unprecedented crises for public health. Coronaviruses are constantly evolving, and it is unknown which new coronavirus will emerge and when the next coronavirus will sweep across the world. Knowledge graphs are expected to help discover the pathogenicity and transmission mechanism of viruses. Objective The aim of this study was to discover potential targets and candidate drugs to repurpose for coronaviruses through a knowledge graph–based approach. Methods We propose a computational and evidence-based knowledge discovery approach to identify potential targets and candidate drugs for coronaviruses from biomedical literature and well-known knowledge bases. To organize the semantic triples extracted automatically from biomedical literature, a semantic conversion model was designed. The literature knowledge was associated and integrated with existing drug and gene knowledge through semantic mapping, and the coronavirus knowledge graph (CovKG) was constructed. We adopted both the knowledge graph embedding model and the semantic reasoning mechanism to discover unrecorded mechanisms of drug action as well as potential targets and drug candidates. Furthermore, we have provided evidence-based support with a scoring and backtracking mechanism. Results The constructed CovKG contains 17,369,620 triples, of which 641,195 were extracted from biomedical literature, covering 13,065 concept unique identifiers, 209 semantic types, and 97 semantic relations of the Unified Medical Language System. Through multi-source knowledge integration, 475 drugs and 262 targets were mapped to existing knowledge, and 41 new drug mechanisms of action were found by semantic reasoning, which were not recorded in the existing knowledge base. Among the knowledge graph embedding models, TransR outperformed others (mean reciprocal rank=0.2510, Hits@10=0.3505). A total of 33 potential targets and 18 drug candidates were identified for coronaviruses. Among them, 7 novel drugs (ie, quinine, nelfinavir, ivermectin, asunaprevir, tylophorine, Artemisia annua extract, and resveratrol) and 3 highly ranked targets (ie, angiotensin converting enzyme 2, transmembrane serine protease 2, and M protein) were further discussed. Conclusions We showed the effectiveness of a knowledge graph–based approach in potential target discovery and drug repurposing for coronaviruses. Our approach can be extended to other viruses or diseases for biomedical knowledge discovery and relevant applications.

According to the World Health Organization (WHO), in the second half of 2022, there are about 606 million confirmed cases of COVID-19 and almost 6,500,000 deaths around the world. A pandemic was declared by the WHO in March 2020 when the new coronavirus spread around the world. The short time between the first cases in Wuhan and the declaration of a pandemic initiated the search for ways to stop the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or to attempt to cure the disease COVID-19. More than ever, research groups are developing vaccines, drugs, and immunobiological compounds, and they are even trying to repurpose drugs in an increasing number of clinical trials. There are great expectations regarding the vaccine’s effectiveness for the prevention of COVID-19. However, producing sufficient doses of vaccines for the entire population and SARS-CoV-2 variants are challenges for pharmaceutical industries. On the contrary, efforts have been made to create different vaccines with different approaches so that they can be used by the entire population. Here, we summarize about 8162 clinical trials, showing a greater number of drug clinical trials in Europe and the United States and less clinical trials in low-income countries. Promising results about the use of new drugs and drug repositioning, monoclonal antibodies, convalescent plasma, and mesenchymal stem cells to control viral infection/replication or the hyper-inflammatory response to the new coronavirus bring hope to treat the disease.

The highly contagious coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic and public health emergency as it has taken the lives of over 5.7 million in more than 180 different countries. This disease is characterized by respiratory tract symptoms, such as dry cough and shortness of breath, as well as other symptoms, including fever, chills, and fatigue. COVID-19 is also characterized by the excessive release of cytokines causing inflammatory injury to the lungs and other organs. It is advised to undergo precautionary measures, such as vaccination, social distancing, use of masks, hygiene, and a healthy diet. This review is aimed at summarizing the pathophysiology of COVID-19 and potential biologically active compounds (bioactive) found in plants and plant food. We conclude that many plant food bioactive compounds exhibit antiviral and anti-inflammatory properties and support in attenuating organ damage due to reduced cytokine release and improving the recovery process from COVID-19 infection.