Chemistry and Biology of SARS-CoV-2

Abstract

SARS-CoV-2 (previously 2019-nCoV or Wuhan coronavirus) caused an unprecedented fast-spreading worldwide pandemic. Although currently with a rather low mortality rate, the virus spread rapidly over the world using the modern world's traffic highways. The coronavirus (CoV) family members were responsible for several deadly outbreaks and epidemics during the last decade. Not only governments but also the scientific community reacted promptly to the outbreak, and information is shared quickly. For example, the genetic fingerprint was shared, and the 3D structure of key proteins was rapidly solved, which can be used for the discovery of potential treatments. An overview is given on the current knowledge of the spread, disease course, and molecular biology of SARS-CoV-2. We discuss potential treatment developments in the context of recent outbreaks, drug repurposing, and development timelines. SARS-CoV-2 OUTBREAK IN WUHANIn December 2019, an outbreak of pneumonia of an unknown cause was reported in Wuhan, in Hubei province, China. It was speculated that the first patient caught the infection from a seafood market that also traded wild animals. The causing agent was quickly identified as a novel coronavirus (CoV). The CoV responsible for the outbreak is now called SARS-CoV-2. The respiratory illness caused by SARS-CoV-2 is called COVID-19. The symptoms of the SARS-CoV-2 infection range from asymptomatic to mild to severe to death. 1 It soon became clear that personto-person transmission was also occurring, as was the case with the previous human CoV. In an unprecedented documented speed, the SARS-CoV-2 travels around the globe, and as of May 15 th led to >4.5 million infections and 300,000 fatalities. Based on the previous experience with the SARS-CoV outbreak at the beginning of this century, very stringent measures were taken by the Chinese government, and several multimillion-inhabitant cities were isolated and put under quarantine in order to slow the pandemic spread. Different hosts of the SARS-CoV-2 are proposed, including snails, bats, and pangolins. 2 CoVs are a large family of zoonotic viruses and their outbreaks are common to humans, although major outbreaks have been experienced in animals, especially in cattle. Under the electron microscope, they exhibit formations that are reminiscent of the solar corona. The common cold is often caused by human CoVs. They are single-stranded enveloped positive RNA viruses and stand out because of their rather large genome. As with viruses in general, the structure is rather simple. SARS-CoV-2 is generally less pathogenic than SARS-CoV, much less pathogenic than the Middle East respiratory syndrome MERS-CoV, but more pathogenic than practically harmless HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63. The reported case-fatality rate of COVID-19 is %3% and is thus rather low as compared with SARS (30%, Table 1). However, the transmission rate (TR) (number of newly infected people per infected person) of 2.5 to 3 is high and accounts

Molecular Basis of SARS-CoV-2 Infection and Rational Design of Potential Antiviral Agents: Modeling and Simulation Approaches

“…30 000 nucleobases, it encodes a relatively low number of proteins, which can be divided into structural and nonstructural proteins ( Figure 8 ). 159 Whereas structural proteins are required to generate viral particles, 16 nonstructural proteins (Nsp1–16) are responsible for the diverse virus functionalities, mainly focusing on replication and survival in the host cell. SARS-CoV-2, such as other betacoronaviruses, translates, once inside the host cell, two overlapping polyproteins (pp1a and pp1ab) that are responsible for encoding all nonstructural and structural proteins.…”

The Ugi Three‐Component Reaction; a Valuable Tool in Modern Organic Synthesis

“…Examples of medicinally active compounds with N-functionalized isatins include CB 2 inverse agonists [197,198] or the Src homology-2 domain containing protein tyrosine phosphatase (Shp2) inhibitors. [199] Another example can be spotted in noncovalent SARS corona virus 3C-like protease inhibitors, [200][201][202] Moreover, there are natural products that contain isatins and structurally related oxindoles, mainly the welwitindolinone series. [203] Hulme et al, [197] synthesized a series of isatins by employing the U-3CR/oxidative deamination strategy.…”

Uses of ethyl benzoyl acetate for the synthesis of thiophene, pyran, and pyridine derivatives with antitumor activities

“…As per the early report in 1850 by Strecker [ 16 ] , this well‐known concept [ 17 ] , also widely represented in nature, has been extensively used in both liquid‐phase [ 14 ] and solid‐phase [ 18 ] chemistry for the rapid assembly of complex heterocyclic structures of importance for pharmaceutical development [ 19 ] . Isocyanide‐based reactions were used as a base of MCRs [ 20–24 ] , in addition Passerini and coworkers reported MCRs [ 25,26 ] to produce diversity of heterocyclic derivatives [ 27 ] . Early appearing in 1882, the well‐known Hantzsch's dihydropyridine synthesis [ 28 ] using 1,3‐dicarbonyl derivatives as one of the first substrate classes involved in a MCR and such reaction received many attentions within the field of organic synthesis.…”