Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019‐nCoV

Abstract

With the current trajectory of the 2019‐nCoV outbreak unknown, public health and medicinal measures will both be needed to contain spreading of the virus and to optimize patient outcomes. Although little is known about the virus, an examination of the genome sequence shows strong homology with its better‐studied cousin, SARS‐CoV. The spike protein used for host cell infection shows key nonsynonymous mutations that might hamper the efficacy of previously developed therapeutics but remains a viable target for the development of biologics and macrocyclic peptides. Other key drug targets, including RNA‐dependent RNA polymerase and coronavirus main proteinase (3CLpro), share a strikingly high (>95 %) homology to SARS‐CoV. Herein, we suggest four potential drug candidates (an ACE2‐based peptide, remdesivir, 3CLpro‐1 and a novel vinylsulfone protease inhibitor) that could be used to treat patients suffering with the 2019‐nCoV. We also summarize previous efforts into drugging these targets and hope to help in the development of broad‐spectrum anti‐coronaviral agents for future epidemics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges

“…Several potential drug candidates, including lopinavir/ritonavir (Kaletra R ), nucleoside analogues, neuraminidase inhibitors, remdesivir, umifenovir (Arbidol R ), DNA synthesis inhibitors (such as tenofovir disoproxil and lamivudine), chloroquine and Chinese traditional medicines (such as ShuFeng JieDu or Lianhua Qingwen capsules), have been proposed [36 , 37] . In addition, an angiotensin-converting enzyme 2 (ACE2)-based peptide, 3CLpro inhibitor (3CLpro-1) and a novel vinylsulfone protease inhibitor, theoretically, appear to show potential for antiviral activity against SARS-CoV-2 [38] . Chloroquine has been well described with in vitro effects on inhibition of uncoating and/or alteration of posttranslational modifications of newly synthesised proteins, especially inhibition of glycosylation in many viruses, including human immunodeficiency virus (HIV) [39] .…”

Arguments in favour of remdesivir for treating SARS-CoV-2 infections

“…So far, no drugs, monoclonal antibodies, or vaccines have been approved to treat human infections due to coronaviruses. Several pre-existing and potential drug candidates, including chloroquine and remdesivir, have been considered [10][11][12]. The discovery and marketing of 4 new compounds often require months to years.…”

“…Though little is known about SARS-CoV-2, several insights may be gained from its more well-known family member, SARS-CoV [11]. Here, we review the literature on an existing but not approved antiviral agent, remdesivir, which exhibits promising in vitro antiviral activity and preliminary clinical experiences in the treatment of COVID-19.…”

“…Although SARS-CoV and SARS-CoV-2 share only 82% RNA sequence identify, their RNA-dependent RNA polymerase (RdRp) share 96% sequence identify [11]. Therefore, the drugs targeting viral RdRp proteins of SARS-CoV are likely to be effective for SARS-CoV-2.…”

Remdesivir as a possible therapeutic option for the COVID-19

“…With the emergence of the SARS-CoV-2, the etiologic agent of (COVID-19), we are in a need for an effective antiviral agent to be able to halt the current outbreak. It had been suggested that remdesivir might be an option for the therapy of patients with COVID-19 [10]. In a case report, remdisivir reatment was started intravenous on day 7 in a patient with COVID-19 [11].…”