The recent outbreak of novel coronavirus pneumonia (COVID-19) caused by a new coronavirus has posed a great threat to public health. Identifying safe and effective antivirals is of urgent demand to cure the huge number of patients. Virus-encoded proteases are considered potential drug targets. The human immunodeficiency virus protease inhibitors (lopinavir/ritonavir) has been recommended in the global Solidarity Trial in March launched by World Health Organization. However, there is currently no experimental evidence to support or against its clinical use. We evaluated the antiviral efficacy of lopinavir/ritonavir along with other two viral protease inhibitors in vitro, and discussed the possible inhibitory mechanism in silico. The in vitro to in vivo extrapolation was carried out to assess whether lopinavir/ritonavir could be effective in clinical. Among the four tested compounds, lopinavir showed the best inhibitory effect against the novel coronavirus infection. However, further in vitro to in vivo extrapolation of pharmacokinetics suggested that lopinavir/ritonavir could not reach effective concentration under standard dosing regimen [marketed as Kaletra^®, contained lopinavir/ritonavir (200 mg/50 mg) tablets, recommended dosage is 400 mg/10 mg (2 tablets) twice daily]. This research concluded that lopinavir/ritonavir should be stopped for clinical use due to the huge gap between in vitro IC₅₀ and free plasma concentration. Nevertheless, the structure–activity relationship analysis of the four inhibitors provided further information for de novel design of future viral protease inhibitors of SARS-CoV-2.

Pulmonary hypertension is a chronic disease developing progressively with high mortality. Pulmonary hypertension patients need persistent medical care; however, limited reports focused on them when there was an outbreak of coronavirus disease 2019 in China. This national survey was aimed to evaluate the overall condition of pulmonary hypertension patients during this period. A questionnaire regarding the living condition of pulmonary hypertension patients during coronavirus disease 2019 was designed by pulmonary hypertension diagnostic experts in Wuhan Asia Heart Hospital. Pulmonary hypertension patients and their family members were invited to participate in this survey online. One‐hundred twenty pulmonary hypertension patients and 23 family members participated in the survey; 64.8% (n = 87) participants came from Hubei, and others were from 15 other provinces; 98.6% (n = 141) participants were in home quarantine; 65.8% (n = 79) were pulmonary arterial hypertension associated with congenital heart disease; and 76.7% (n = 92) patients proclaimed their heart function was well maintained at class I or II. One (0.8%) patient was confirmed severe acute respiratory syndrome coronavirus 2 infection. Two (1.7%) patients were hospitalized due to heart function worsening. Nearly 70% (n = 100) participants implied shortage in medications during coronavirus disease 2019 outbreak. A total of 24.2% (n = 29) patients indicated that medications were discontinued due to the insufficient supply. Most of the participants stayed optimistic on either coronavirus disease 2019 outbreak or their pulmonary hypertension disease, and 61.7% (n = 74) patients would go to the hospital for follow‐up immediately after outbreak. These preliminary data show pulmonary hypertension patients are able to avoid severe disease when they are in home quarantine. Medication supplement is important for pulmonary hypertension patients when their heart function is well maintained. In addition, there might be increasing requirements of medical care for pulmonary hypertension patients after the outbreak.

As of August 23, 2020, the 2019 novel coronavirus disease (COVID-19) has infected more than 23,518,340 people and caused more than 810,492 deaths worldwide including 4,717 deaths in China. We present a case of a 53-year-old woman who was admitted to the hospital because of dry coughs and high fever on January 26, 2020, in Wuhan, China. She was not tested for SARS-CoV-2 RNA until on hospital day 11 (illness day 21) because of a significant shortage of test kits at the local hospital. Then, her test was positive for COVID-19 on hospital day 20. Despite intensive medical treatments, she developed respiratory failure with secondary bacterial infection and expired on hospital day 23 (3 days after she was tested positive for SARS-CoV-2 RNA). A systemic autopsy examination, including immunohistochemistry and ultrastructural studies, demonstrates that SARS-CoV-2 can infect multiple organs with profound adverse effect on the immune system, and the lung pathology is characterized by diffuse alveolar damage. Extrapulmonary SARS-CoV-2 RNA was detected in several organs postmortem. The detailed pathological features are described. In addition, this report highlights the value of forensic autopsy in studying SARS-CoV-2 infection and the importance of clinicopathological correlation in better understanding the pathogenesis of COVID-19.

The ongoing COVID-19 pandemic has caused over six million deaths and huge economic burdens worldwide. Antivirals against its causative agent, SARS-CoV-2, are in urgent demand. Previously, we reported that heterocylic compounds, i.e., chloroquine (CQ) and hydroxychloroquine (HCQ), are potent in inhibiting SARS-CoV-2 replication in vitro. In this study, we discussed the syntheses of two novel heterocylic compounds: tert-butyl rel-4-(((3R,4S)-3-(1H-indol-3-yl)-1-oxo-2-propyl-1,2,3,4-tetrahydroisoquinolin-4-yl)methyl)piperazine-1-carboxylate (trans-1) and rel-(3R,4S)-3-(1H-indol-3-yl)-4-(piperazin-1-ylmethyl)-2-propyl-3,4-dihydroisoquinolin-1(2H)-one (trans-2), which effectively suppressed authentic SARS-CoV-2 replication in Vero E6 cells. Compound trans-1 showed higher anti-SARS-CoV-2 activity than trans-2, with a half maximal effective concentration (EC₅₀) of 3.15 μM and a selective index (SI) exceeding 63.49, which demonstrated comparable potency to CQ or HCQ. Additional anti-SARS-CoV-2 tests on Calu-3 human lung cells showed that trans-1 efficiently inhibited viral replication (EC₅₀ = 2.78 μM; SI: > 71.94) and performed better than CQ (EC₅₀ = 44.90 μM; SI = 2.94). The time of an addition assay showed that the action mechanism of trans-1 differed from that of CQ, as it mainly inhibited the post-entry viral replication in both Vero E6 and Calu-3 cells. In addition, the differences between the antiviral mechanisms of these novel compounds and CQ were discussed.

Two dimensional electron systems (2DES) usually show the weak localization behavior in consequence of electron interaction in the limited dimension. Distinct from other 2DES, the monolayer graphene, due to the chirality, exhibits unique weak localization behavior sensitive to not only inelastic but also elastic carrier scattering. Grain boundaries, which usually exist in monolayer graphene, are apparently related to the elastic carrier scattering process, thus affecting the weak localization behavior. However, their effect is scarcely studied due to the lack of an ideal platform. Here, a complementary system consisting of both single-crystalline graphene grown on Ge (110) and poly-crystalline graphene grown on Ge (111) is constructed. From the comparison of magnetoresistivity measurements, the weak localization effect is found to be greatly enhanced for the poly-crystalline graphene on Ge(111) compared to the single-crystalline graphene on Ge(110). The degraded transport performance in graphene/Ge(111) is due to the presence of grain boundary in poly-crystalline graphene, which results in the enhanced elastic intervalley scattering. In addition, the inelastic scattering originating from the strong electron-electron interaction at low temperature also contributes to weak localization of poly-crystalline graphene/Ge(111).