Potential therapeutic agents against COVID-19: What we know so far.

The emerging outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 continues to spread all over the world. Agents or vaccines of proven efficacy to treat or prevent human coronavirus infection are in urgent need and are being investigated vigorously worldwide. This review summarizes the current evidence of potential therapeutic agents, such as lopinavir/ritonavir, remdesivir, favipiravir, chloroquine, hydroxychloroquine, interferon, ribavirin, tocilizumab, and sarilumab. More clinical trials are being conducted for further confirmation of the efficacy and safety of these agents in treating COVID-19.

Tetrandrine selectively protects against amyloid-beta protein - but not against MPTP-induced cytotoxicity in SK-N-SH neuroblastoma cells.

The evidence for loss of Ca2+ homeostasis due to neuronal degeneration is considerable and rapidly increasing. In this study, we try to evaluate the protective effect of tetrandrine (TET), an alkaloid isolated from the Chinese medicinal herb Radix Stephania tetrandrae S., on amyloid-beta protein (Abeta) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced cell death in SK-N-SH neuroblastoma cells. Both compounds reduced cell viability in a concentration-dependent manner after 72 h in culture. Cell proliferation in the presence of 20 microM Abeta or 0.4 mM MPTP was reduced to 58.3 +/- 4.9 or 54.9 +/- 5.5 %, respectively. TET (0.1, 0.5 and 1 microM) alone had no significant effect on cell survival; however, it prevented Abeta-induced cell death in a concentration-dependent manner. In contrast, TET failed to counteract MPTP-induced cytotoxicity. Also, an L-type calcium channel blocker, nimodipine, solely reversed Abeta-induced cell death. On the other hand, ELISA determination of mono-/oligo-nucleosomes accumulation showed that the mode of cell death evoked by Abeta was necrosis while that evoked by MPTP was presumably apoptosis. These results suggest that TET may mitigate the harmful effects of Abeta on cell survival, probably by interfering via the necrotic signal related to Ca2+ overloading through the L-type calcium channel.

Divergent role of calcium on Abeta- and MPTP-induced cell death in SK-N-SH neuroblastoma.

We attempted to clarify the role of Ca2+ in cell death caused by beta-amyloid protein (Abeta) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in SK-N-SH neuroblastoma, respectively. Two insults both reduced cell viability in a concentration-dependent manner and induced equal cytotoxicity in the presence of 20 microM Abeta and 0.4 mM MPTP for 72 h, respectively (68+/-7 vs. 64+/-6% viability). Time-related study showed that Abeta evoked cell death occurred quickly at 24 h. Relatively, MPTP exhibited a delayed cell death significantly after 72 h of culture. Pretreating the cells with nimodipine and chelating of Ca2+ by EGTA plus 1,2-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) successfully rescued Abeta-induced cell death but failed to prevent MPTP toxicity. ELISA determination of mono/oligonucleosomes accumulation showed the mode of cell death evoked by MPTP was presumably apoptosis while by Abeta was necrosis. SK-N-SH cells constitutively expressed the alpha(1C) subunit of L-type Ca2+ channel and exposure to Abeta or MPTP for 96 h did not further modify its expression. By contrast, alpha(1D) subunit was undetectable or low level expressed in basal condition, but was induced to express after Abeta and MPTP stimulation in a time-dependent manner. Functional assay revealed that KCl-evoked [Ca2+]i rise was significantly greater in Abeta-, but not in MPTP-treated cells when compared with control. Taken together, these results showed that Abeta and MPTP elicited different mode of cell death in SK-N-SH. Nevertheless, Ca2+ overload seems to solely display a crucial role in Abeta-induced cytotoxicity and over-expressed alpha(1D) may contribute to the disruption of cellular Ca2+ homeostasis.