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BackgroundArtesunate is an antimalarial agent with broad anti-cancer activity in in vitro and animal experiments and case reports. Artesunate has not been studied in rigorous clinical trials for anticancer effects.AimTo determine the anticancer effect and tolerability of oral artesunate in colorectal cancer (CRC).MethodsThis was a single centre, randomised, double-blind, placebo-controlled trial. Patients planned for curative resection of biopsy confirmed single primary site CRC were randomised (n = 23) by computer-generated code supplied in opaque envelopes to receive preoperatively either 14 daily doses of oral artesunate (200 mg; n = 12) or placebo (n = 11). The primary outcome measure was the proportion of tumour cells undergoing apoptosis (significant if > 7% showed Tunel staining). Secondary immunohistochemical outcomes assessed these tumour markers: VEGF, EGFR, c-MYC, CD31, Ki67 and p53, and clinical responses.Findings20 patients (artesunate = 9, placebo = 11) completed the trial per protocol. Randomization groups were comparable clinically and for tumour characteristics. Apoptosis in > 7% of cells was seen in 67% and 55% of patients in artesunate and placebo groups, respectively. Using Bayesian analysis, the probabilities of an artesunate treatment effect reducing Ki67 and increasing CD31 expression were 0.89 and 0.79, respectively. During a median follow up of 42 months 1 patient in the artesunate and 6 patients in the placebo group developed recurrent CRC.InterpretationArtesunate has anti-proliferative properties in CRC and is generally well tolerated.

Coronavirus disease 2019 (COVID-19) is a major threat worldwide due to its fast spreading. As yet, there are no established drugs or vaccines available. Speeding up drug discovery is urgently required. We applied a workflow of combined in silico methods (virtual drug screening, molecular docking and supervised machine learning algorithms) to identify novel drug candidates against COVID-19. We constructed chemical libraries consisting of FDA-approved drugs for drug repositioning and of natural compound datasets from literature mining and the ZINC database to select compounds interacting with SARS-CoV-2 target proteins (spike protein, nucleocapsid protein, and 2'-o-ribose methyltransferase). Supported by the supercomputer MOGON II, candidate compounds were predicted as presumable SARS-CoV-2 inhibitors. Interestingly, several approved drugs against hepatitis C virus (HCV), another enveloped (-) ssRNA virus (paritaprevir, simeprevir, grazoprevir, and velpatasvir) as well as drugs against transmissible diseases, against cancer, or other diseases were identified as candidates against SARS-CoV-2. This result is supported by reports that anti-HCV compounds are also active against Middle East Respiratory Virus Syndrome (MERS) coronavirus. The candidate compounds identified by us may help to speed up the drug development against SARS-CoV-2.

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Coronavirus disease 2019 (COVID-19) is a major threat worldwide due to its fast spreading. As yet, there are no established drugs or vaccines available. Speeding up drug discovery is urgently required. We applied a workflow of combined in silico methods (virtual drug screening, molecular docking and supervised machine learning algorithms) to identify novel drug candidates against COVID-19. We constructed chemical libraries consisting of FDA-approved drugs for drug repositioning and of natural compound datasets from literature mining and the ZINC database to select compounds interacting with SARS-CoV-2 target proteins (spike protein, nucleocapsid protein, and 2’-o-ribose methyltransferase). Supported by the supercomputer MOGON, candidate compounds were predicted as presumable SARS-CoV-2 inhibitors. Interestingly, several approved drugs against hepatitis C virus (HCV), another enveloped (-) ssRNA virus (paritaprevir, simeprevir and velpatasvir) as well as drugs against transmissible diseases, against cancer, or other diseases were identified as candidates against SARS-CoV-2. This result is supported by reports that anti-HCV compounds are also active against Middle East Respiratory Virus Syndrome (MERS) coronavirus. The candidate compounds identified by us may help to speed up the drug development against SARS-CoV-2.