Identification of alpha-linolenic acid as a broad-spectrum antiviral against zika, dengue, herpes simplex, influenza virus and SARS-CoV-2 infection.

Zika virus (ZIKV) has garnered global attention due to its association with severe congenital defects including microcephaly. However, there are no licensed vaccines or drugs against ZIKV infection. Pregnant women have the greatest need for treatment, making drug safety crucial. Alpha-linolenic acid (ALA), a polyunsaturated ω-3 fatty acid, has been used as a health-care product and dietary supplement due to its potential medicinal properties. Here, we demonstrated that ALA inhibits ZIKV infection in cells without loss of cell viability. Time-of-addition assay revealed that ALA interrupts the binding, adsorption, and entry stages of ZIKV replication cycle. The mechanism is probably that ALA disrupts membrane integrity of the virions to release ZIKV RNA, inhibiting viral infectivity. Further examination revealed that ALA inhibited DENV-2, HSV-1, influenza virus and SARS-CoV-2 infection dose-dependently. ALA is a promising broad-spectrum antiviral agent.

Tetrahydropyrimidines, ZL-5015 Alleviated Lipopolysaccharide (LPS)-Induced Acute Pneumonia in Rats by Activating the NRF-2/HO-1 Pathway.

BACKGROUND Acute pneumonia is a severe inflammatory disease of the respiratory system. Drugs used to treat acute pneumonia often have strong side effects. Recent studies have shown that tetrahydropyrimidines, ZL-5015 has anti-inflammatory and antitumor effects. However, whether ZL-5015 can relieve symptoms of acute pneumonia is unclear. MATERIAL AND METHODS In this study, we used lipo-polysaccharide (LPS) to stimulate SD rats to simulate conditions of acute pneumonia. Diverse doses of ZL-5015 were used for treatment of these rats. After the rates were sacrificed, serum, lung tissue, and bronchoalveolar lavage fluid were collected for the next study. Hematoxylin-eosin (H&E) staining then was used to detect pathologic changes in lung tissues. Enzyme-linked immunosorbent assay was performed to assess levels of inflammatory factors in serum. Commercial kits were used to assess levels of reactive oxygen species (ROS) in bronchoalveolar lavage fluid. RESULTS Treatment of ZL-5015 relieved stenosis of the alveolar space and pulmonary edema. Furthermore, levels of inflammatory factors (TNF-alpha, IL-1ß and IL-18) in the lung tissues and serum were downregulated after treatment with ZL-5015. Production of ROS also was suppressed after application of ZL-5015. Moreover, inhibition of expression of NRF-2 and HO-1 was relieved after treatment with ZL-5015. The therapeutic effect of ZL-5015 showed a dose-response relationship. CONCLUSIONS ZL-5015 alleviated LPS-induced inflammatory injury and oxidative damage by activating the NRF-2/HO-1 pathway.

Bioinformatics analysis of the structure and function of NADPH-cytochrome p450 reductase of Plasmodium vivax.

The structure of NADPH-cytochrome p450 reductase (CPR) of Plasmodium falciparum (P. falciparum or Pf) has been determined using bioinformatics analysis. However, that of Plasmodium vivax (P. vivax or Pv) has not yet been determined. This study aimed to analyze the structure and function of PvCPR using bioinformatics analysis. The results demonstrated that PvCPR was an unstable and alkaline enzyme located in the cytoplasm of parasites with a signal peptide. It possessed seven types of signal sites and eight protein-protein binding sites, and had a tertiary structure resembling a forceps with a single wing, which differed from that of PfCPR. It also had nine linear B-cell epitopes and 10 antigenicity sites, which were not homologous with the amino acid sequence of Homo sapiens (H. sapiens or Hs) CPR and six fragments that were similar to fragments of immune-related protein sequences from H. sapiens. Therefore, the function of PvCPR may be different from that of PfCPR, and PvCPR may participate in the immune escape of P. vivax.

Serious diarrhea with weight loss caused by Capillaria philippinensis acquired in China: a case report.

BACKGROUND: Diarrhea caused by Capillaria philippinensis (C. philippinensis) has not been reported in any areas with the exception of Taiwan province in China. We herein report the misdiagnosis and subsequent management of a patient with diarrhea caused by C. philippinensis. CASE PRESENTATION: A 33-year-old woman from the outskirts of Danzhou city, Hainan province, China, had an 11-month history of chronic diarrhea with abdominal pain, edema, hypoalbuminemia, and severe weight loss. The patient was misdiagnosed at an outpatient clinic and one hospital. She was finally correctly diagnosed with C. philippinensis by stool examination. The patient was given a 30-days course of albendazole (400 mg/day) and had an uneventful and stable recovery. CONCLUSION: Doctors cannot lose sight of patients' dietary histories, must query stool examination results, and need to expand their knowledge of certain nonlocal and global diseases, especially those described in new case reports. Some diagnostic examinations must be performed repeatedly. Hainan province may be the epidemic focus of C. philippinensis.

Bioinformatics analysis and prediction for structure and function of nitric oxide synthase and similar proteins from Plasmodium berghei.

OBJECTIVE: To search and analyze nitric oxide synthase (NOS) and similar proteins from Plasmodium berghei(Pb). METHODS: The structure and function of nitric oxide synthase and similar proteins from Plasmodium berghei were analyzed and predicted by bioinformatics. RESULTS: PbNOS were not available, but nicotinamide adenine dinucleotide 2'-phosphate reduced tetrasodium (NADPH)-cytochrome p450 reductase(CPR) were gained. PbCPR was in the nucleus of Plasmodium berghei, while 134aa-229aa domain was localize in nucleolar organizer. The amino acids sequence of PbCPR had the closest genetic relationship with Plasmodium vivax showing a 73% homology. The tertiary structure of PbCPR displayed the forcep-shape with wings, but no wings existed in the tertiary structure of its' host, Mus musculus(Mm). 137aa-200aa, 201aa-218aa, 220aa-230aa, 232aa-248, 269aa-323aa, 478aa-501aa and 592aa-606aa domains of PbCPR showed no homology with MmCPRs', and all domains were exposed on the surface of the protein. CONCLUSIONS: NOS can't be found in Plasmodium berghei and other Plasmodium species. PbCPR may be a possible resistance site of antimalarial drug, and the targets of antimalarial drug and vaccine. It may be also one of the mechanisms of immune evasion. This study on Plasmodium berghei may be more suitable to Plasmodium vivax. And 137aa-200aa, 201aa-218aa, 220aa-230aa, 232aa-248, 269aa-323aa, 478aa-501aa and 592aa-606aa domains of PbCPR are more ideal targets of antimalarial drug and vaccine.

Bioinformatics analysis for structure and function of CPR of Plasmodium falciparum.

OBJECTIVE: To analyse the structure and function of NADPH-cytochrome p450 reductase (CYPOR or CPR) from Plasmodium falciparum (Pf), and to predict its' drug target and vaccine target. METHODS: The structure, function, drug target and vaccine target of CPR from Plasmodium falciparum were analyzed and predicted by bioinformatics methods. RESULTS: PfCPR, which was older CPR, had close relationship with the CPR from other Plasmodium species, but it was distant from its hosts, such as Homo sapiens and Anopheles. PfCPR was located in the cellular nucleus of Plasmodium falciparum. 335aa-352aa and 591aa - 608aa were inserted the interior side of the nuclear membrane, while 151aa-265aa was located in the nucleolus organizer regions. PfCPR had 40 function sites and 44 protein-protein binding sites in amino acid sequence. The teriary structure of 1aa-700aa was forcep-shaped with wings. 15 segments of PfCPR had no homology with Homo sapien CPR and most were exposed on the surface of the protein. These segments had 25 protein-protein binding sites. While 13 other segments all possessed function sites. CONCLUSIONS: The evolution or genesis of Plasmodium falciparum is earlier than those of Homo sapiens. PfCPR is a possible resistance site of antimalarial drug and may involve immune evasion, which is associated with parasite of sporozoite in hepatocytes. PfCPR is unsuitable as vaccine target, but it has at least 13 ideal drug targets.