In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.

Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion.Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC 50 of 24.86 μg/mL and IC 50 of 15.16 μg/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85×10 -7 M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.

CpG repression in RNA viruses has been known for decades, but a reasonable explanation has not yet been proposed to explain this phenomenon. In this study, we calculated the CpG odds ratio of all RNA viruses that have available genome sequences and analyzed the correlation with their genome polarity, base composition, synonymous codon usage, phylogenetic relationship, and host. The results indicated that the viral base composition, synonymous codon usage and host selection were the dominant factors that determined the CpG bias in RNA viruses. CpG usage variation between the different viral groups was caused by different combinations of these pressures, which also differed from each other in strength. The consistent under-representation of CpG usage in −ssRNA viruses is determined predominantly by base composition, which may be a consequence of the U/A preferred mutation bias of −ssRNA viruses, whereas the CpG usage of +ssRNA viruses is affected greatly by their hosts. As a result, most +ssRNA viruses mimic their hosts' CpG usage. Unbiased CpG usage in dsRNA viruses is most likely a result of their dsRNA genome, which allows the viruses to escape from the host-driven CpG elimination pressure. CpG was under-represented in all reverse-transcribing viruses (RT viruses), suggesting that DNA methylation is an important factor affecting the CpG usage of retroviruses. However, vertebrate-infecting RT viruses may also suffer host' CpG elimination pressure that also acts on +ssRNA viruses, which results in further under-representation of CpG in the vertebrate-infecting RT viruses.

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Peripheral blood and mucosal compartments are equally responsive to effective antiretroviral therapies. The detection of significant changes within 7 days of starting antiviral therapy implies that intestinal dysfunction may be a direct result of local HIV infection.

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The present studies were undertaken to compare the relative pharmacokinetic parameters and bioavailability of two chemically related natural products which are nonnucleoside inhibitors of reverse transcriptase. Both (+)-calanolide A (Cal A; NSC 675451) and (+)-dihydrocalanolide A (DHCal A; NSC 678323) are currently under development for the treatment of HIV infections. HPLC-based analytical assays were developed for both compounds using modifications of a previously published procedure. The assays were used to compare the intravenous pharmacokinetics of the dihydro analogue relative to the parent compound, Cal A, and to determine the relative oral bioavailability of each drug in CD2F1 mice. Although the pharmacokinetic parameters of each drug were similar (Cal A, 25 mg/kg: AUC: 9.4 [microg/mL]. hr, t1/2beta: 0.25 h,, t1/2gamma: 1.8 h, clearance: 2.7 L/h/kg versus DHCal A, 25 mg/kg: AUC: 6.9 [microg/mL].hr, t1/2beta: 0.22 h,, t1/2gamma: 2.3 h, clearance: 3.6 L/h/kg), the oral bioavailability of DHCal A (F = 46. 8%) was markedly better than that obtained for Cal A (F = 13.2%). The relative ability of Cal A and DHCal A to change to their inactive epimer forms, (+)-calanolide B and (+)-dihydrocalanolide B, respectively, was also determined. While conversion of active to inactive forms of the drugs was noted to occur in vitro especially under acidic conditions, no epimer forms of either compound were noted in plasma of mice after administration of either CalA or DHCal A. Considered together with preliminary toxicology findings, the pharmacokinetic data obtained in the present series of experiments suggest that selection of the dihydro derivative of (+)-calanolide A may be a reasonable choice for further preclinical development and possible Phase I clinical evaluation.

and Fang J. (2019). "Studying the mix design and investigating the photocatalytic performance of pervious concrete containing TiO2-soaked recycled aggregates."