Predicting In Vitro and In Vivo Anti-SARS-CoV-2 Activities of Antivirals by Intracellular Bioavailability and Biochemical Activity.

Cellular drug response (concentration required for obtaining 50% of a maximum cellular effect, EC50) can be predicted by the intracellular bioavailability (F ic) and biochemical activity (half-maximal inhibitory concentration, IC50) of drugs. In an ideal model, the cellular negative log of EC50 (pEC50) equals the sum of log F ic and the negative log of IC50 (pIC50). Here, we measured F ic's of remdesivir, favipiravir, and hydroxychloroquine in various cells and calculated their anti-SARS-CoV-2 EC50's. The predicted EC50's are close to the observed EC50's in vitro. When the lung concentrations of antiviral drugs are higher than the predicted EC50's in alveolar type 2 cells, the antiviral drugs inhibit virus replication in vivo, and vice versa. Overall, our results indicate that both in vitro and in vivo antiviral activities of drugs can be predicted by their intracellular bioavailability and biochemical activity without using virus. This virus-free strategy can help medicinal chemists and pharmacologists to screen antivirals during early drug discovery, especially for researchers who are not able to work in the high-level biosafety lab.

Influence and Control of SARS-CoV-2 Transmission under Two Different Models

SARS-CoV-2 is transmitted by contacting;however, the virus is so active that it can attach to objects and be transmitted from objects to humans via such contacting. The virus, which spreads through some living or inanimate-mediated processes, is more dangerous. On the basis of the routine contact transmission of infectious diseases, this paper further discusses the scope and efficiency of infectious diseases with indirect transmission. Through the study of two different transmission routes, the dynamic models of infectious diseases were constructed. The propagation of these two processes is theoretically studied using a differential equation model and stability analysis theory, and some actual virus propagation processes are simulated by numerical solutions. The prevention and control methods of infectious diseases are given, which lay the theoretical foundation for the discussion of related problems in practical application.

Glycyrrhizin Inhibits SARS-CoV-2 Entry into Cells by Targeting ACE2.

Coronavirus Disease 2019 (COVID-19) is a highly infectious and pathogenic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early in this epidemic, the herbal formulas used in traditional Chinese medicine (TCM) were widely used for the treatment of COVID-19 in China. According to Venn diagram analysis, we found that Glycyrrhizae Radix et Rhizoma is a frequent herb in TCM formulas against COVID-19. The extract of Glycyrrhizae Radix et Rhizoma exhibits an anti-SARS-CoV-2 replication activity in vitro, but its pharmacological mechanism remains unclear. We here demonstrate that glycyrrhizin, the main active ingredient of Glycyrrhizae Radix et Rhizoma, prevents the coronavirus from entering cells by targeting angiotensin-converting enzyme 2 (ACE2). Glycyrrhizin inhibited the binding of the spike protein of the SARS-CoV-2 to ACE2 in our Western blot-based assay. The following bulk RNA-seq analysis showed that glycyrrhizin down-regulated ACE2 expression in vitro which was further confirmed by Western blot and quantitative PCR. Together, we believe that glycyrrhizin inhibits SARS-CoV-2 entry into cells by targeting ACE2.

The Impacts of Medical Resources on Emerging Self-Limiting Infectious Diseases

The spread of emerging self-limiting infectious diseases is closely related to medical resources. This paper introduces the concept of safe medical resources, i.e., the minimum medical resources that are needed to prevent the overburden of medical resources, and explores the impacts of medical resources on the spread of emerging self-limiting infectious diseases. The results showed that when the isolation rate of hospitalized patients who have mild infections is low, increasing the isolation rate of patients with severe infections requires safe more medical resources. On the contrary, when the isolation rate of hospitalized patients with mild infections is at a high level, increasing the isolation rate of patients with severe infections results in a decrease in safe medical resources. Furthermore, when the isolation rates of patients with mild and severe infections increase simultaneously, safe medical resources decrease gradually. That is to say, when the medical resources are at a low level, it is more necessary to improve the isolation rates of infected individuals so as to avoid the phenomenon of overburdened medical resources and control the spread of emerging infectious diseases. In addition, overwhelmed medical resources increase the number of deaths. Meanwhile, for different emerging self-limiting infectious diseases, as long as the recovery periods are the same, safe medical resources also remain the same.

The effect of quarantine measures for close contacts on the transmission of emerging infectious diseases with infectivity in incubation period

For emerging infectious disease with infectivity in incubation period, this paper studies the effect of quarantine measures for close contacts on the transmission of emerging infectious disease with the help of the differential equation model. The results show that as long as measures where close contacts are quarantined are taken, when to take measures is a very important factor. Under a given quarantine intensity, there is a phase transition structure about the start time of taking measures. Only when the start time of taking measure is earlier than the first critical moment of phase transition, the final cumulative number of patients and deaths can be stabilized in low level, so as to control the spread of epidemics. At the same time, whenever quarantine measures are taken, even if the quarantine intensity is not strong enough, the peak value of existing infectious individuals will decrease and the duration when the number of existing infectious individuals is high will be shortened, and the final cumulative number of patients and deaths will be significantly reduced.

Influence of isolation measures for patients with mild symptoms on the spread of COVID-19.

During the transmission of COVID-19, the hospital isolation of patients with mild symptoms has been a concern. In this paper, we use a differential equation model to describe the propagation of COVID-19, and discuss the effects of intensity of hospital isolation and moment of taking measures on development of the epidemic. The results show that isolation measures can significantly reduce the epidemic final size and the number of dead, and the greater the intensity of measures, the better, but duration of the epidemic will be prolonged. Whenever isolation measures are taken, the epidemic final size and the number of dead can be reduced. In early stage of the epidemic, taking measures one day later has little impact, but after a certain period, if taking measures one day later, the epidemic final size and the number of dead increase sharply. Taking measures as early as possible makes the maximum number of patients appear later, which is conducive to expanding medical bed resources and reducing the pressure on medical resource demand. As long as possible, high-intensity isolation measures should be taken in time for patients with mild symptoms.