In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initialWuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including favipiravir, a broad-spectrum antiviral drug that interferes with the viral replication, and hydroxychloroquine, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis.
Conclusions
In this article, we present an overview of the current state of knowledge on the SARS-CoV-2 and COVID-19 pandemic. In addition to an overview of the epidemiological, clinical, and radiological features of SARS-CoV-2 (Figure 1), we also summarize possible therapeutic options currently under investigation and the future outlook for the disease. We also speculate on several mechanisms contributing to the novel profile of COVID-19 pneumonia, including its high transmissibility caused by unvaried ACE2 structure at the viral binding site among different populations, and its unique progression pattern, in which patients could be asymptomatic, yet presenting positive radiographic or laboratory findings.
We summarize the current clinical trials that have been rapidly initiated upon the onset of the pandemic emergency and are currently undergoing as for April 2020. Most of them are based on repurposing the therapeutic agents previously designed for other applications. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. Whereas the vaccines and therapeutic antibodies aimed to specifically target SARS-CoV-2 are also being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, drug repurposing happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety, and have demonstrated their action against other viruses, including the related SARS-CoV and MERS-CoV. These drugs target different viral infection response pathways, or directly interfere with the virus replication cycle as summarized in Figure 2. As for now, some of them have already demonstrated promising results in the initial clinical trials performed in the wake of the pandemic and have been approved for a wider use. The promising examples include favipiravir, an influenza drug that interferes with the viral replication, and hydroxychloroquine, a repurposed antimalarial drug that interferes with the virus endosomal entry pathway.
By posing a significant challenge toward the public health system and the existing antiviral strategies, SARS-CoV-2 has undoubtedly grabbed the globe’s attention in the beginning of 2020. We believe this may be a trigger for more systematic approaches to prepare ourselves in advance for any potential future pandemics. In the era of big data, more systematic approaches to identify the potential agents for drug repurposing can be applied. Noteworthy is the recent study by Zhou et al., whereby an integrative analysis of interactome networks associated with human coronaviruses and drugs targeting the components of these networks was applied to reveal 16 novel candidates for drug repurposing [86].
We believe that such computational techniques combined with the follow-up experimental studies aimed to test the computationally predicted antiviral agents can help us to have a wider arsenal of potentially repurposed drugs in the case of any future virus outbreaks.
Reference & source information : https://www.mdpi.com/
Read More on :