A significant proportion of viral pandemics occur following zoonotic transmission events, where animal-associated viruses jump species into human populations. In order to provide forewarnings of the emergence of these viruses, it is necessary to develop a better understanding of what determines virus host range, often at the genetic and structural levels. In this study, we demonstrated that the small-ruminant morbillivirus, a close relative of measles, is unable to use human receptors to enter cells; however, a change of a single amino acid in the virus is sufficient to overcome this restriction. This information will be important for monitoring this virus’s evolution in the field. Of note, this study was undertaken in vitro, without generation of a fully infectious virus with this phenotype.
We report the computational and experimental efforts in the design and synthesis of novel neuraminidase (NA) inhibitors from ferulic acid and vanillin. Two proposed ferulic acid analogues, MY7 and MY8 were predicted to inhibit H1N1 NA using molecular docking. From these two analogues, we designed, synthesised and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. The enzymatic H1N1 NA inhibition assay showed MY21 (a vanillin derivative) has the lowest IC50 of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50 of ~0.95 μM. Modelling studies further suggest that these predicted activities might be due to the interactions with conserved and essential residues of NA with ΔGbind values comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors.
BackgroundElectroacupuncture (EA) is believed to modulate the pain pathway via the release of endogenous opioid substances and stimulation of descending pain inhibitory pathways. In this study, the use of intraoperative 2 Hertz EA stimulation is investigated to determine any opioid-sparing effect and reduction of postoperative nausea and vomiting (PONV) in patients undergoing gynaecological surgery.Patient and MethodsThis was a prospective, double blinded randomized study conducted in a tertiary hospital in Malaysia. Patients (n = 64) were randomly allocated to receive 2 Hertz EA and compared to a control group. EA was started intraoperatively till the end of the surgery (mean duration of surgery was 149.06 ± 42.64 minutes) under general anaesthesia. Postoperative numerical rating scale (NRS), the incidence of nausea, vomiting and usage of rescue antiemetics were recorded at 30 minutes, 2, 4, and 24 hours, respectively. The total morphine demand and usage from the patient-controlled analgesia Morphine (PCAM) were also recorded in the first 24 hours postoperatively.ResultsThe mean NRS was 2.75 (SD = 2.34) at 30 minutes and 2.25 (SD = 1.80) at 2 hours postoperatively in the EA group that was significantly lower than the mean NRS in the control group as 4.50 (SD = 2.37) at 30 minutes and 3.88 (SD = 2.21) at 2 hours. The mean PCA morphine demand was 27.28 (SD = 21.61) times pressed in the EA group and 55.25 (SD = 46.85) times pressed in the control group within 24 hours postoperatively, which showed a significant reduction in the EA group than the control group. Similarly, total morphine requirement was significantly lower in the EA group with the value of 21.38 (SD = 14.38) mg compared to the control group with the value of 33.94 (SD = 20.24) mg within 24 hours postoperatively. Incidence of postoperative nausea also significantly reduced in the EA group at 30 minutes (15.6%) compared to the control group (46.9%).ConclusionsIt can be concluded that subjects receiving EA intraoperatively experienced less pain and PONV. Hence, it is plausible that EA has an opioid-sparing effect and can reduce PONV.
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