Targeting the SARS-CoV-2 main protease: Vaccines are an important tool in the fight against COVID-19, but developing antiviral drugs is also a high priority, especially with the rise of variants that may partially evade vaccines. The viral protein main protease is required for cleaving precursor polyproteins into functional viral proteins. This essential function makes it a key drug target. Qiao et al. designed 32 inhibitors based on either boceprevir or telaprevir, both of which are protease inhibitors approved to treat hepatitis C virus. Six compounds protected cells from viral infection with high potency, and two of these were selected for in vivo studies based on pharmokinetic experiments. Both showed strong antiviral activity in a mouse model. Science , this issue p. 1374

SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity. Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments. Mast cells (MCs) are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations. In this study, we showed that SARS-CoV-2-triggered MC degranulation initiated alveolar epithelial inflammation and lung injury. SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques, and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells; MC degranulation altered various signaling pathways in alveolar epithelial cells, particularly, the induction of pro-inflammatory factors and consequential disruption of tight junctions. Importantly, the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury. These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation, and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.

Co-infection with HIV and HCV and/or HBV is highly prevalent in intravenous drug users (IDUs). Because of the proximity to the “Golden Triangle”, HIV prevalence among the IDUs is very high in the China-Myanmar border region. However, there are few studies about co-infection with HIV and HCV and/or HBV, especially in the region that belongs to Myanmar. 721 IDUs, including 403 Chinese and 318 Burmese, were investigated for their HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) serological status. Statistical analysis was performed to evaluate the differences of the epidemic situation between the Chinese IDUs and the Burmese IDUs. Among the Chinese IDUs and the Burmese IDUs, HCV infection was the most prevalent (69.0% vs 48.1%, P<0.001), followed by HBV (51.6% vs 43.1%, P0.05). Besides, there were more HIV-HBV co-infected IDUs (20.1% vs 11.3%, P<0.005), and HIV-HCV co-infected IDUs (31.8% vs 23.9%, P<0.05) in China than in Myanmar, as well as HIV-HBV-HCV triple infection (19.1% vs 10.4%, P<0.005). Co-infection with HIV and HCV and/or HBV is highly prevalent among the IDUs in the China-Myanmar border region. The HIV epidemic appears to be in a downward trend, compared with previous reports. However, all infections were more prevalent among the Chinese IDUs than among the Burmese.

To estimate the prevalence of HIV, HCV, HBV and co-infection with 2 or 3 viruses and evaluate risk factors among injecting drug users (IDUs) in Yunnan province, China. 2080 IDUs were recruited from 5 regions of Yunnan Province, China to detect the infection status of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). Statistical analysis was performed to evaluate risk factors related to HIV, HCV and HBV infections. The infection rates among all participants were 25.5% for HIV, 77.7% for HCV, 19.2% for HBV, 15% for HIV/HCV, 0.3% for HIV/HBV, 7.8% for HCV/HBV and 7.1% for HIV/HCV/HBV. The prevalence of virus infection varied widely by region in Yunnan of China. Statistical analyses indicated that high prevalence of HIV and HCV among IDUs was positively associated with the duration of drug injection and sharing needles/syringes; besides, HCV infection was associated with the frequency of drug injection. HIV, HCV, HBV infections and co-infections were still very prevalent among IDUs in Yunnan province because of drug use behaviors.

Objective: To investigate the subtype characterization of HIV-1 among IDUs in northern Myanmar. Design: A molecular epidemiological investigation was conducted among IDUs in Laza and Maizayang cities of northern Myanmar. Methods: A total of 83 HIV-1-positive serums were collected from consenting IDUs during June to August 2009. HIV-1 p17, pol, vif-env, C2V3 fragments were amplified and sequenced. Phylogenetic and bootscanning analyses were performed. Results: A very high proportion (86.1%) of HIV-1 intersubtype recombinants and very low proportion of subtypes B′ (3.8%), C (7.6%) and CRF01_AE (1.3%) were found in this HIV-infected IDUs cohort. These recombinants cover all four kinds of recombination forms formed among CRF01_AE, B and C. The B/C and CRF01_AE/B/C recombinants are the two most dominant recombinants, accounting for 54.4 and 42.6% of all cases, respectively, and indicating the ongoing generation of extensive and complex HIV-1 recombination among CRF01_AE, B′ and C in northern Myanmar. Intriguingly, most recombinants have different chimeric patterns from each other, forming 64 unique recombination forms (URFs) that are quite distinct from any previously identified circulating recombinant forms (CRFs) and URFs in Asia. Conclusion: The extremely high proportion of intersubtype recombinants, especially CRF01_AE/B′/C recombinants (42.6%), strongly suggests that northern Myanmar is a big forge for HIV-1 recombination among CRF01_AE, B′ and C.