Nafamostat mesylate treatment in combination with favipiravir for patients critically ill with Covid-19: a case series

Development of specific therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently required. Several drugs such as antimalarial and anti-Ebola virus drugs are under investigation for coronavirus disease 2019 (Covid-19). Transmembrane protease serine 2 (TMPRSS2) plays a crucial role for SARS-CoV-2 entry into the cytoplasm [1]. Inhibition of TMPRSS2 protease activity is assumed to prohibit viral entry of SARS-CoV-2. Through high-throughput screening of 1017 existing drugs, a clinically available serine protease inhibitor nafamostat mesylate was identified as a potent inhibitor of Middle East respiratory syndrome coronavirus entry into human epithelial cells [2]. More recently, nafamostat mesylate was shown to inhibit the entry of SARS-CoV-2 into the human epithelial cells at EC50 of ~ 10 nM [3, 4]. Nafamostat mesylate has been clinically used for the treatment of acute pancreatitis and disseminated intravascular coagulation in Japan. By intravenous administration, its blood concentrations are maintained at 30–240 nM, which are sufficient to block the virus entry [3]. An anti-influenza A H1N1 virus drug favipiravir exhibits antiviral activity against other RNA viruses and therefore is expected to have antiviral action against SARS-CoV-2. This drug has been approved in Japan for novel influenza virus disease

The association between adverse reactions and immune response against SARS-CoV-2 spike protein after vaccination with BNT162b2 among healthcare workers in a single healthcare system: a prospective observational cohort study

Adverse reactions after vaccination with COVID-19 mRNA vaccines are common; however, the association between adverse reactions and humoral responses is uncertain. To determine whether humoral immune responses after BNT162b2 vaccine administration were associated with local and systemic adverse reactions, we conducted a prospective observational cohort study in a single tertiary referral center. Healthcare workers who received the first dose of BNT162b2 vaccine were recruited. SARS-CoV-2 anti-spike IgG antibody titers were measured three weeks after the second dose and information about adverse reactions after vaccination was collected. Among the 887 participants, 641 (72.3%) were women. The median age was 38 (range, 22–74) years. All but one showed anti-spike IgG levels well above the cutoff, with a median level of 13,600 arbitrary units/mL. Overall, 800 (92.2%) participants reported some reactions after the first dose and 822 (96.3%) after the second dose. Significantly more participants reported systemic reactions after the second dose than after the first dose (P < .01), and 625 (73.6%) reported that reactions were stronger after the second dose. Factors positively associated with elevation of anti-spike IgG levels were history of asthma (24% higher if present, P = .01) and stronger reactions after the second dose (19% higher if experienced, P = .02). The majority of participants showed good humoral responses and reported some adverse reactions after vaccination. Anti-spike IgG levels were significantly higher if adverse reactions after the second dose were stronger than those after the first dose. These findings may help inform current and future vaccine recipients

A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans.

The APOBEC3 deaminases are potent inhibitors of virus replication and barriers to cross-species transmission. For simian immunodeficiency virus (SIV) to transmit to a new primate host, as happened multiple times to seed the ongoing HIV-1 epidemic, the viral infectivity factor (Vif) must be capable of neutralizing the APOBEC3 enzymes of the new host. Although much is known about current interactions of HIV-1 Vif and human APOBEC3s, the evolutionary changes in SIV Vif required for transmission from chimpanzees to gorillas and ultimately to humans are poorly understood. Here, we demonstrate that gorilla APOBEC3G is a factor with the potential to hamper SIV transmission from chimpanzees to gorillas. Gain-of-function experiments using SIVcpzPtt Vif revealed that this barrier could be overcome by a single Vif acidic amino acid substitution (M16E). Moreover, degradation of gorilla APOBEC3F is induced by Vif through a mechanism that is distinct from that of human APOBEC3F. Thus, our findings identify virus adaptations in gorillas that preceded and may have facilitated transmission to humans