Since the emergence of a novel coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported from Wuhan, China, neither a specific vaccine nor an antiviral drug against SARS-CoV-2 has become available. However, a combination of two HIV-1 protease inhibitors, lopinavir and ritonavir, has been found to be effective against SARS-CoV, and both drugs could bind well to the SARS-CoV 3C-like protease (SARS-CoV 3CL pro ). In this work, molecular complexation between each inhibitor and SARS-CoV-2 3CL pro was studied using all-atom molecular dynamics simulations, free energy calculations, and pair interaction energy analyses based on MM/PB(GB)SA and FMO-MP2/PCM/6-31G* methods. Both anti-HIV drugs interacted well with the residues at the active site of SARS-CoV-2 3CL pro . Ritonavir showed a somewhat higher number atomic contacts, a somewhat higher binding efficiency, and a somewhat higher number of key binding residues compared to lopinavir, which correspond with the slightly lower water accessibility at the 3CL pro active site. In addition, only ritonavir could interact with the oxyanion hole residues N142 and G143 via the formation of two hydrogen bonds. The interactions in terms of electrostatics, dispersion, and charge transfer played an important role in the drug binding. The obtained results demonstrated how repurposed anti-HIV drugs could be used to combat COVID-19.

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Outbreaks of trichinellosis caused by Trichinella papuae have been reported in SouthEast Asia. Mebendazole and thiabendazole are the treatments of choice for trichinellosis; however, both drugs result in significant side effects and are less effective for muscle-stage larvae (L1). An alternative therapeutic agent is needed to improve treatment. Information on lipid composition and metabolic pathways may bridge gaps in our knowledge and lead to new antiparasitics. The T. papuae L1 lipidome was analysed using a mass spectrometry-based approach, and 403 lipid components were identified. Eight lipid classes were found and glycerophospholipids were dominant, corresponding to 63% of total lipids, of which the glycerolipid DG (20:1[11Z]/22:4[7Z,10Z,13Z,16Z]/0:0) (iso2) was the most abundant. Overall, 57% of T. papuae lipids were absent in humans; therefore, lipid metabolism may be dissimilar in the two species. Proteins involved T. papuae lipid metabolism were explored using bioinformatics. We found that 4-hydroxybutyrate coenzyme A transferase, uncharacterized protein (A0A0V1MCB5) and ML-domain-containing protein are not present in humans. T. papuae glycerophospholipid metabolic and phosphatidylinositol dephosphorylation processes contain several proteins that are dissimilar to those in humans. These findings provide insights into T. papuae lipid composition and metabolism, which may facilitate the development of novel trichinellosis treatments. Trichinella is a genus of parasitic roundworms that cause trichinosis, also known as trichinellosis, which infect domestic and sylvatic animals. The number of global outbreaks appears to have sharply increased, reflecting changes in the parasites' epidemiology 1. In SouthEast Asia, outbreaks of trichinellosis caused by T. papuae occurred in 2006 2 and 2007 3. T. papuae, which belongs to the non-encapsulated trichinella clade, lives predominantly in tropical rainforests 4. Ingestion of raw meat containing parasite cysts leads to infection, and the larvae released from adult females invade host muscles resulting in trichinellosis pathology. Common symptoms are eye puffiness, splinter haemorrhaging, nonspecific gastroenteritis, and muscle pain 5. Trichinosis treatment is based on anti-inflammatory drugs and anthelmintics, such as mebendazole and albendazole 6 ; however, the effectiveness of anthelmintic treatment is an issue of debate. In the treatment of myositis during a trichinellosis outbreak in Thailand, mebendazole and thiabendazole were found to be more efficient than placebo or fluconazole. However, 30% of volunteers could not tolerate the side effects of thiabendazole 7. In addition, in a trial during an outbreak in Italy, between 3% and 45% of patients had a recurrence of various symptoms after a 10-day mebendazole course 8. Generally, anthelmintic therapy is only considered effective during the intestinal phase of infection, and the drug has poor drug effectiveness in the muscle phase 9. To improve the effectiveness of the treatment, an alternative therapeutic agent may...

Schistosoma mekongi is one of the major causative agents of human schistosomiasis in Southeast Asia. Praziquantel is now the only drug available for treatment and there are serious concerns about parasite resistance to it. Therefore, a dataset of schistosome targets is necessary for drug development. Phosphorylation regulates signalling pathways to control cellular processes that are important for the parasite’s growth and reproduction. Inhibition of key phosphoproteins may reduce the severity of schistosomiasis. In this research, we studied the phosphoproteomes of S . mekongi male and female adult worms by using computational and experimental approaches. Using a phosphoproteomics approach, we determined that 88 and 44 phosphoproteins were male- and female-biased, respectively. Immunohistochemistry using anti-phosphoserine antibodies demonstrated phosphorylation on the tegument and muscle of male S . mekongi worms and on the vitelline gland and gastrointestinal tract of female worms. This research revealed S . mekongi sex-dependent phosphoproteins. Our findings provide a better understanding of the role of phosphorylation in S . mekongi and could be integrated with information from other Schistosoma species to facilitate drug and vaccine development.