a b s t r a c tOnly a month after the outbreak of pneumonia caused by 2019-nCoV, more than forty-thousand people were infected. This put enormous pressure on the Chinese government, medical healthcare provider, and the general public, but also made the international community deeply nervous. On the 25th day after the outbreak, the Chinese government implemented strict traffic restrictions on the area where the 2019-nCoV had originateddHubei province, whose capital city is Wuhan. Ten days later, the rate of increase of cases in Hubei showed a significant difference (p ¼ 0.0001) compared with the total rate of increase in other provinces of China. These preliminary data suggest the effectiveness of a traffic restriction policy for this pandemic thus far. At the same time, solid financial support and improved research ability, along with network communication technology, also greatly facilitated the application of epidemic prevention measures. These measures were motivated by the need to provide effective treatment of patients, and involved consultation with three major groups in policy formulationdpublic health experts, the government, and the general public. It was also aided by media and information technology, as well as international cooperation. This experience will provide China and other countries with valuable lessons for quickly coordinating and coping with future public health emergencies.
A novel swine-origin pandemic influenza A(H1N1) virus (H1N1pdm, also referred to as S-OIV) was identified as the causative agent of the 21st century's first influenza pandemic, but molecular features conferring its ability of human-to-human transmission has not been identified. Here we compared the protein sequences of 2009 H1N1pdm strains with those causing other pandemics and the viruses isolated from humans, swines and avians, and then analyzed the mutation trend of the residues at the signature and non-signature positions, which are species- and non-species-associated, respectively, in the proteins of H1N1pdm during the pandemic of 2009. We confirmed that the host-specific genomic signatures of 2009 H1N1pdm, which are mainly swine-like, were highly identical to those of the 1918 H1N1pdm. During the short period of time when the pandemic alert level was raised from phase 4 to phase 6, one signature residue at the position of NP-100 mutated from valine to isoleucine. Four non-signature residues, at positions NA-91, NA-233, HA-206, and NS1-123, also changed during the epidemic in 2009. All these mutant residues, except that at NA-91, are located in the viral functional domains, suggesting that they may play roles in the human adaption and virulence of 2009 H1N1pdm.
BackgroundMost currently approved anti-HIV drugs (e.g., reverse transcriptase inhibitors, protease inhibitors and fusion/entry inhibitors) must act inside or on surface of the target cell to inhibit HIV infection, but none can directly inactivate virions away from cells. Although soluble CD4 (sCD4) can inactivate laboratory-adapted HIV-1 strains, it fails to reduce the viral loads in clinical trials because of its low potency against primary isolates and tendency to enhance HIV-1 infection at low concentration. Thus, it is essential to design a better HIV inactivator with improved potency for developing new anti-HIV therapeutics that can actively attack the virus in the circulation before it attaches to and enter into the target cell.ResultsWe engineered a bivalent HIV-1 inactivator, designated 2DLT, by linking the D1D2 domain of CD4 to T1144, the next generation HIV fusion inhibitor, with a 35-mer linker. The D1D2 domain in this soluble 2DLT protein could bind to the CD4-binding site and induce the formation of the gp41 prehairpin fusion-intermediate (PFI), but showed no sCD4-mediated enhancement of HIV-1 infection. The T1144 domain in 2DLT then bound to the exposed PFI, resulting in rapid inactivation of HIV-1 virions in the absence of the target cell. Beside, 2DLT could also inhibit fusion of the virus with the target cell if the virion escapes the first attack of 2DLT.ConclusionThis bivalent molecule can serve as a dual barrier against HIV infection by first inactivating HIV-1 virions away from cells and then blocking HIV-1 entry on the target cell surface, indicating its potential for development as a new class of anti-HIV drug.
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