Linagliptin for COVID-19

Drug repurposing has emerged as a promising strategy in the rapid development of effective therapeutics for COVID-19. This approach leverages existing medications, previously approved for other indications, to target the pathophysiological mechanisms of SARS-CoV-2 infection. Several drugs were tested during the COVID-19 pandemic, developed originally for other purposes and under less-than-ideal conditions. Some of the most well-known include remdesivir, an Ebola drug approved by the FDA for emergency use to treat COVID-19, and dexamethasone, a corticosteroid that reduces death associated with severe infection through immunomodulation. However, while hydroxychloroquine and ivermectin, among others, showed very meager or no benefit, it is clear that such early promise must be subjected to firm testing. Despite such promises, drug repurposing may face several inconsistent clinical outcomes, questions over safety, and the inability to address all forms of COVID-19 pathology. Key candidates identified through high-throughput screening and computational methods include antiviral agents, anti-inflammatory drugs, and those targeting host cell pathways critical for viral replication. This review discusses the efficacy and mechanisms of these repurposed drugs, highlights ongoing clinical trials, and addresses challenges such as resistance and optimal dosing. Ultimately, drug repurposing represents a crucial component of the multi-faceted response required to combat the COVID-19 pandemic effectively.

The coronavirus disease 2019 (COVID-19) is a severe worldwide pandemic. Due to the emergence of various SARS-CoV-2 variants and the presence of only one Food and Drug Administration (FDA) approved anti-COVID-19 drug (remdesivir), the disease remains a mindboggling global public health problem. Developing anti-COVID-19 drug candidates that are effective against SARS-CoV-2 and its various variants is a pressing need that should be satisfied. This systematic review assesses the existing literature that used in silico models during the discovery procedure of anti-COVID-19 drugs. Cochrane Library, Science Direct, Google Scholar, and PubMed were used to conduct a literature search to find the relevant articles utilizing the search terms “In silico model,” “COVID-19,” “Anti-COVID-19 drug,” “Drug discovery,” “Computational drug designing,” and “Computer-aided drug design.” Studies published in English between 2019 and December 2022 were included in the systematic review. From the 1120 articles retrieved from the databases and reference lists, only 33 were included in the review after the removal of duplicates, screening, and eligibility assessment. Most of the articles are studies that use SARS-CoV-2 proteins as drug targets. Both ligand-based and structure-based methods were utilized to obtain lead anti-COVID-19 drug candidates. Sixteen articles also assessed absorption, distribution, metabolism, excretion, toxicity (ADMET), and drug-likeness properties. Confirmation of the inhibitory ability of the candidate leads by in vivo or in vitro assays was reported in only five articles. Virtual screening, molecular docking (MD), and molecular dynamics simulation (MDS) emerged as the most commonly utilized in silico models for anti-COVID-19 drug discovery.

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.

Abstract Background For both the current and future pandemics, there is a need for high-throughput drug screening methods to identify existing drugs with potential preventative and/or therapeutic activity. Epidemiologic studies could complement lab-focused efforts to identify possible therapeutic agents. Methods We performed a pharmacopeia-wide association study (PWAS) to identify commonly prescribed medications and medication classes that are associated with the detection of SARS-CoV-2 in older individuals (>65 years) in long-term care homes (LTCH) and the community, between January 15 th, 2020 and December 31 st, 2020, across the province of Ontario, Canada. Results 26,121 cases and 2,369,020 controls from LTCH and the community were included in this analysis. Many of the drugs and drug classes evaluated did not yield significant associations with SARS-CoV-2 detection. However, some drugs and drug classes appeared significantly associated with reduced SARS-CoV-2 detection, including cardioprotective drug classes such as statins (weighted OR 0.91, standard p-value <0.01, adjusted p-value <0.01) and beta-blockers (weighted OR 0.87, standard p-value <0.01, adjusted p-value 0.01), along with individual agents ranging from levetiracetam (weighted OR 0.70, standard p-value <0.01, adjusted p-value <0.01) to fluoxetine (weighted OR 0.86, standard p-value 0.013, adjusted p-value 0.198) to digoxin (weighted OR 0.89, standard p-value <0.01, adjusted p-value 0.02). Conclusions Using this epidemiologic approach which can be applied to current and future pandemics we have identified a variety of target drugs and drug classes that could offer therapeutic benefit in COVID-19 and may warrant further validation. Some of these agents (e.g. fluoxetine) have already been identified for their therapeutic potential.