Structures of SARS-CoV-2 RNA-Binding Proteins and Therapeutic Targets

Muhammad Tahir Khan, Muhammad Irfan, Hina Ahsan, Abrar Ahmed, Aman Chandra Kaushik, Anwar Sheed Khan, Sathishkumar Chinnasamy, Arif Ali, Dong Qing Wei

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations

Abstract

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemic has resulted in thousands of infections and deaths worldwide. Several therapies are currently undergoing clinical trials for the treatment of SARS-CoV-2 infection. However, the development of new drugs and the repositioning of existing drugs can only be achieved after the identification of potential therapeutic targets within structures, as this strategy provides the most precise solution for developing treatments for sudden epidemic infectious diseases. Summary: In the current investigation, crystal and cryo-electron microscopy structures encoded by the SARS-CoV-2 genome were systematically examined for the identification of potential drug targets. These structures include nonstructural proteins (Nsp-9; Nsp-12; and Nsp-15), nucleocapsid (N) proteins, and the main protease (Mpro). Key Message: The structural information reveals the presence of many potential alternative therapeutic targets, primarily involved in interaction between N protein and Nsp3, forming replication-transcription complexes (RTCs) which might be a potential drug target for effective control of current SARS-CoV-2 pandemic. RTCs consist of 16 nonstructural proteins (Nsp1-16) that play the most essential role in the synthesis of viral RNA. Targeting the physical linkage between the envelope and single-stranded positive RNA, a process facilitated by matrix proteins may provide a good alternative strategy. Our current study provides useful information for the development of new lead compounds against SARS-CoV-2 infections.

Original languageEnglish
Pages (from-to)55-68
Number of pages14
JournalIntervirology
Volume64
Issue number2
DOIs
StatePublished - 1 Apr 2021
Externally publishedYes

Keywords

  • Inhibitors
  • M
  • Nsp-15
  • Nsp-9
  • Nsp12
  • Targets

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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