evere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of coronavirus disease 2019 (COVID-19), with over 84.66 million infections and 1.83 million deaths as reported on 3 January 2021 (refs. 1,2). SARS-CoV-2 is a positive-sense, single-stranded RNA virus. SARS-CoV-2 and several related beta-coronaviruses, including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), are highly pathogenic. Infections can lead to severe acute respiratory syndrome, loss of lung function and, in severe cases, death. Compared to SARS-CoV and MERS-CoV, SARS-CoV-2 has a higher capacity of human-to-human infections, which resulted in the rapidly growing pandemic 3. Finding an effective treatment for COVID-19, potentially also through drug repurposing, is an urgent but unmet medical need. Suramin (Fig. 1a) is a century-old drug that has been used to treat African sleeping sickness and river blindness 4,5. It has also been shown to be effective in inhibiting the replication of a wide range of viruses, including enteroviruses 6 , Zika virus 7 , Chikungunya 8 and Ebola viruses 9. The viral inhibition mechanisms of suramin are diverse, including inhibition of viral attachment, viral entry and release from host cells in part through interactions with viral capsid proteins 7,8,10,11. Recently, suramin has been shown to inhibit SARS-CoV-2 infection in cell culture by preventing cellular entry of the virus 12. Here we report that suramin is also a potent inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), an essential enzyme for the viral life cycle. The potency of suramin in biochemical RdRp inhibition assays is at least 20-fold more potent than remdesivir, the current Food and Drug Administration-approved nucleotide drug for the treatment of COVID-19. The activity of suramin in cell-based viral inhibition is similar to remdesivir because the highly negative charge of suramin prevents efficient cellular uptake. A cryogenic electron microscopy (cryo-EM) structure reveals that suramin binds to the RdRp active site, blocking the binding of both RNA template and primer strands. These results provide a structural template for the design of next generation suramin derivatives as SARS-CoV-2 RdRp inhibitors. Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin Wanchao Yin 1,

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Kaposi’s sarcoma (KS), a highly disseminated tumor of hyperproliferative spindle endothelial cells, is the most common AIDS-associated malignancy caused by infection of Kaposi’s sarcoma-associated herpesvirus (KSHV). KSHV-encoded viral interferon regulatory factor 1 (vIRF1) is a viral oncogene but its role in KSHV-induced tumor invasiveness and motility remains unknown. Here, we report that vIRF1 promotes endothelial cell migration, invasion and proliferation by down-regulating miR-218-5p to relieve its suppression of downstream targets high mobility group box 2 (HMGB2) and cytidine/uridine monophosphate kinase 1 (CMPK1). Mechanistically, vIRF1 inhibits p53 function to increase the expression of DNA methyltransferase 1 (DNMT1) and DNA methylation of the promoter of pre-miR-218-1, a precursor of miR-218-5p, and increases the expression of a long non-coding RNA OIP5 antisense RNA 1 (lnc-OIP5-AS1), which acts as a competing endogenous RNA (ceRNA) of miR-218-5p to inhibit its function and reduce its stability. Moreover, lnc-OIP5-AS1 increases DNA methylation of the pre-miR-218-1 promoter. Finally, deletion of vIRF1 from the KSHV genome reduces the level of lnc-OIP5-AS1, increases the level of miR-218-5p, and inhibits KSHV-induced invasion. Together, these results define a novel complex lnc-OIP5-AS1/miR-218-5p network hijacked by vIRF1 to promote invasiveness and motility of KSHV-induced tumors.

With recent emergence of wearable electronic devices, flexible and stretchable transparent electrodes are the core components to realize innovative devices. The copper nanowire (CuNW) network is commonly chosen because of its high conductivity and transparency. However, the junction resistances and low aspect ratios still limit its further stretchable performance. Herein, a large-scale stretchable semiembedded CuNW transparent conductive film (TCF) was fabricated by electrolessly depositing Cu on the electrospun poly(4-vinylpyridine) polymer template semiembedded in polydimethylsiloxane. Compared with traditional CuNWs, which are as-coated on the flexible substrate, the semiembedded CuNW TCFs showed low sheet resistance (15.6 Ω·sq at ∼82% transmittance) as well as outstanding stretchability and mechanical stability. The light-emitting diode connected the stretchable semiembedded CuNW TCFs in the electric circuit still lighted up even after stretching with 25% strain. Moreover, this semiembedded CuNW TCF was successfully applied in polymer solar cells as a stretchable conductive electrode, which yielded a power conversion efficiency of 4.6% with 0.1 cm effective area. The large-scale stretchable CuNW TCFs show potential for the development of wearable electronic devices.

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CO hydrogenation to light alkenes was carried out on manganese promoted iron catalysts prepared by coprecipitation and sol-gel techniques. Addition of manganese in the range of 1-4 mol.% by means of coprecipitation could improve notably the percentage of C 2 = $C 4 = in the products, but it was not so efficient when the sol-gel method was employed. XRD and H 2 -TPR measurements showed that the catalyst samples giving high C 2 = $C 4 = yields possessed ultrafine particles in the form of pure a-(Fe 1-x Mn x ) 2 O 3 , and high quality in lowering the reduction temperature of the iron oxide. Furthermore, these samples displayed deep extent of carburization and different surface procedures to the others in the tests of Temperature Programmed Surface Carburization (TPSC). The different surface procedures of these samples were considered to have close relationship with the evolving of surface oxygen. It was also suggested that for the catalysts with high C 2 = $C 4 = yields, the turnover rate of the active site could be kept at a relatively high level due to the improved reducing and carburizing capabilities. Consequently, there would be a large number of sites for CO adsorption/dissociation and an enhanced carburization environment on the catalyst surface, so that the process of hydrogenation could be suppressed relatively to a low level. As a result, the percentage of the light alkenes in the products could be raised.