The authors included RRIDs in their in Virologica Sinica paper! We value the author's support of reproducibility. #reproducibility #BetterScience #OpenResearch
Host OTUB2 and viral PLpro stabilize NSP8 to promote SARS-CoV-2 replication
Read the full paper: Host OTUB2 and viral PLpro stabilize NSP8 to promote SARS-CoV-2 replication
doi.org
October 8, 2026 at 7:00 AM
The authors included RRIDs in their in Virologica Sinica paper! We value the author's support of reproducibility. #reproducibility #BetterScience #OpenResearch
The authors included RRIDs in their in International Journal of Molecular Sciences paper! RRIDs improve reproducibility in scientific research. #OpenScience #reproducibility #RRID
Genetically Encoded Fluorescent Sensors for SARS-CoV-2 Papain-like Protease PLpro
Read the full paper: Genetically Encoded Fluorescent Sensors for SARS-CoV-2 Papain-like Protease PLpro
doi.org
September 16, 2026 at 7:39 PM
The authors included RRIDs in their in International Journal of Molecular Sciences paper! RRIDs improve reproducibility in scientific research. #OpenScience #reproducibility #RRID
The optimized compound, PH521 (4f), inhibited Mpro without promiscuous activity against other cysteine proteases tested, including PLpro, human CatL, and cruzain. 3/5
September 9, 2026 at 8:20 PM
The optimized compound, PH521 (4f), inhibited Mpro without promiscuous activity against other cysteine proteases tested, including PLpro, human CatL, and cruzain. 3/5
There's a definite tendency toward reversion to bat-CoV AA in Cryptics & certain categories of chronics—including key PLpro muts like ORF1a:F1779L, K1795Q.
Some "bat reversions" used to only show up in chronics but are now widely prevalent/fixed: S:S50L, S:R346T, S:N460K, ORF9b:I5T, etc. Others...
Some "bat reversions" used to only show up in chronics but are now widely prevalent/fixed: S:S50L, S:R346T, S:N460K, ORF9b:I5T, etc. Others...
September 7, 2026 at 7:24 PM
There's a definite tendency toward reversion to bat-CoV AA in Cryptics & certain categories of chronics—including key PLpro muts like ORF1a:F1779L, K1795Q.
Some "bat reversions" used to only show up in chronics but are now widely prevalent/fixed: S:S50L, S:R346T, S:N460K, ORF9b:I5T, etc. Others...
Some "bat reversions" used to only show up in chronics but are now widely prevalent/fixed: S:S50L, S:R346T, S:N460K, ORF9b:I5T, etc. Others...
Southern Medical University. Two nanobodies blocked SARS-CoV-2 PLpro at the ISG15 interface, suppressing viral replication and inflammatory signals in cells and mice.
A dual antiviral and immune mechanism.
journals.asm.org/doi/10.1128/...
A dual antiviral and immune mechanism.
journals.asm.org/doi/10.1128/...
Nanobodies targeting SARS-CoV-2 papain-like protease exert dual antiviral and anti-inflammatory effects | Journal of Virology
The COVID-19 pandemic caused by SARS-CoV-2 has resulted in millions of deaths worldwide. Despite the emergence of antiviral drugs and vaccines targeting 3CLpro and RNA-dependent RNA polymerase (Rdrp), the virus’s continuous mutation underscores the need for novel therapeutic approaches that target highly conserved viral regions. PLpro is an attractive target due to its roles in viral replication and host immune regulation. However, research on nanobodies targeting PLpro remains in its infancy. This study provides significant insights into the antiviral and anti-inflammatory functions of two nanobodies, NbP1 and NbP2, which specifically disrupt the PLpro/ISG15 interaction interface. Our findings have important implications for drug development targeting SARS-CoV-2, highlighting the potential of nanobody-based therapeutics to simultaneously inhibit viral replication and suppress pathological inflammation.
journals.asm.org
August 28, 2026 at 3:09 PM
Southern Medical University. Two nanobodies blocked SARS-CoV-2 PLpro at the ISG15 interface, suppressing viral replication and inflammatory signals in cells and mice.
A dual antiviral and immune mechanism.
journals.asm.org/doi/10.1128/...
A dual antiviral and immune mechanism.
journals.asm.org/doi/10.1128/...
National Facility for Protein Science in Shanghai screened 820 fragments and found 7 PLpro pockets.
One new site can be occupied alongside the active site, and Frag368 inhibited PLpro at 13.38 μM, a blueprint for dual-site antivirals.
www.jbc.org/article/S002...
One new site can be occupied alongside the active site, and Frag368 inhibited PLpro at 13.38 μM, a blueprint for dual-site antivirals.
www.jbc.org/article/S002...
Discovery of Novel Druggable Binding Pockets on SARS-CoV-2 PLpro via Fragment Screening and Insights for Structure-Based Inhibitor Design
Coronaviruses are a large family of viruses capable of causing severe respiratory
diseases, with recent outbreaks posing major threats to global public health. The
SARS-CoV-2 papain-like protease (PLp...
www.jbc.org
August 15, 2026 at 2:04 PM
National Facility for Protein Science in Shanghai screened 820 fragments and found 7 PLpro pockets.
One new site can be occupied alongside the active site, and Frag368 inhibited PLpro at 13.38 μM, a blueprint for dual-site antivirals.
www.jbc.org/article/S002...
One new site can be occupied alongside the active site, and Frag368 inhibited PLpro at 13.38 μM, a blueprint for dual-site antivirals.
www.jbc.org/article/S002...
Cleveland Clinic. SARS-CoV-2 PLpro removed ISG15 from immune and metabolic proteins, blunting antiviral sensing while restoring fuel and antioxidant defenses that aid replication.
www.cell.com/immunity/ful...
www.cell.com/immunity/ful...
Virus-induced deconjugation of ISG15 dysregulates innate immunity and cellular metabolism
SARS-CoV-2 encodes a viral deISGylase called PLpro, but its physiological functions
and direct substrates remain elusive. Using a deISGylation-activity-ablated recombinant
SARS-CoV-2, Zhu et al. show ...
www.cell.com
August 6, 2026 at 4:37 PM
Cleveland Clinic. SARS-CoV-2 PLpro removed ISG15 from immune and metabolic proteins, blunting antiviral sensing while restoring fuel and antioxidant defenses that aid replication.
www.cell.com/immunity/ful...
www.cell.com/immunity/ful...
Online now: Virus-induced deconjugation of ISG15 dysregulates innate immunity and cellular metabolism
Virus-induced deconjugation of ISG15 dysregulates innate immunity and cellular metabolism
SARS-CoV-2 encodes a viral deISGylase called PLpro, but its physiological functions and direct substrates remain elusive. Using a deISGylation-activity-ablated recombinant SARS-CoV-2, Zhu et al. show that deISGylation activity is required for innate immune evasion and, furthermore, relieves metabolic restriction of viral replication by modulating the activity of key enzymes in glycolysis, the pentose phosphate pathway, and redox homeostasis.
dlvr.it
August 6, 2026 at 2:48 PM
Online now: Virus-induced deconjugation of ISG15 dysregulates innate immunity and cellular metabolism
#SBFM Sunshine Biopharma and University of Arizona Publish Significant New Research Findings
https://www.stocktitan.net/news/SBFM/sunshine-biopharma-and-university-of-arizona-publish-significant-new-1kv0ngz3t5e8.html
https://www.stocktitan.net/news/SBFM/sunshine-biopharma-and-university-of-arizona-publish-significant-new-1kv0ngz3t5e8.html
Sunshine Biopharma and University of Arizona Publish Significant New Research Findings
Sunshine Biopharma (NASDAQ:SBFM) announced peer‑reviewed publication in the Journal of Medicinal Chemistry of research on MR1‑114, a novel noncovalent PLpro inhibitor for SARS‑CoV‑2. MR1‑114 showed nanomolar potency in vitro across multiple variants, including the Washington strain, Delta and Omicron BA.5.According to Sunshine Biopharma, MR1‑114 demonstrated broad‑spectrum activity, favorable ADME properties, high oral bioavailability and preferential lung enrichment in mice and rats. In the K18‑hACE2 mouse model, repeated oral dosing matched the therapeutic efficacy of Nirmatrelvir by significantly suppressing pulmonary viral replication and preventing disease‑associated weight loss.The work, conducted with the University of Arizona, is described as an important milestone in Sunshine Biopharma’s PLpro inhibitor program for SARS Coronavirus infections. The company also highlights a commercial portfolio of 60 generic prescription drugs in Canada, with about 12 additional launches planned for 2026 and a K1.1 mRNA program for liver cancer.
www.stocktitan.net
July 20, 2026 at 12:30 PM
#SBFM Sunshine Biopharma and University of Arizona Publish Significant New Research Findings
https://www.stocktitan.net/news/SBFM/sunshine-biopharma-and-university-of-arizona-publish-significant-new-1kv0ngz3t5e8.html
https://www.stocktitan.net/news/SBFM/sunshine-biopharma-and-university-of-arizona-publish-significant-new-1kv0ngz3t5e8.html
A crystal structure of PLpro exhibits Ubl2 in two distinct conformations: the well characterized closed state, where Ubl2 is positioned near the PLpro domain, and an as yet uncharacterized open state #SARSCoV2 #PapainLikeProteases #Ubl2Domain doi.org/10.1107/S205...
July 15, 2026 at 2:15 PM
A crystal structure of PLpro exhibits Ubl2 in two distinct conformations: the well characterized closed state, where Ubl2 is positioned near the PLpro domain, and an as yet uncharacterized open state #SARSCoV2 #PapainLikeProteases #Ubl2Domain doi.org/10.1107/S205...
Researchers at WSU EACPHS developed promising new antiviral compounds that target the coronavirus PLpro enzyme. Lead candidates demonstrated potent activity against SARS-CoV-2 and may support future broad-spectrum coronavirus therapies. #DrugDiscovery #COVID19Research
doi.org/10.1016/j.ej...
doi.org/10.1016/j.ej...
Redirecting
doi.org
July 13, 2026 at 7:08 PM
Researchers at WSU EACPHS developed promising new antiviral compounds that target the coronavirus PLpro enzyme. Lead candidates demonstrated potent activity against SARS-CoV-2 and may support future broad-spectrum coronavirus therapies. #DrugDiscovery #COVID19Research
doi.org/10.1016/j.ej...
doi.org/10.1016/j.ej...
But the really cool thing is a RF.5.3 sublineage that got 417T (convergently with PQ.16.1.1) and further S:Y453F in this batch! Still very small but it looks one to watch.
Ah ps it has also Orf1a:T1638N (PLPro mut) which is already doing great in another RF.5 branch
github.com/sars-cov-2-v...
Ah ps it has also Orf1a:T1638N (PLPro mut) which is already doing great in another RF.5 branch
github.com/sars-cov-2-v...
RF.5.3 with S:N417T (3, Singapore, Western Australia, UK) with two branches: one with S:W64R (2, Singapore, W.Aus) and the other with S:Y453F (1 , Uk not on Gisaid) · Issue #3481 · sars-cov-2-variants...
RF.5.3 >> ORF1a:T4083M (C12513T), A12841G ,S:N417T (A22812C) >> ORF1a:T1854I (C5826T), C9118T, S:W64R (T21752C) Query: new C12513T, A12841G ,T16908C [ OLD:A12841G, T21752C, A22812C] Samples: 3 Firs...
github.com
July 13, 2026 at 11:13 AM
But the really cool thing is a RF.5.3 sublineage that got 417T (convergently with PQ.16.1.1) and further S:Y453F in this batch! Still very small but it looks one to watch.
Ah ps it has also Orf1a:T1638N (PLPro mut) which is already doing great in another RF.5 branch
github.com/sars-cov-2-v...
Ah ps it has also Orf1a:T1638N (PLPro mut) which is already doing great in another RF.5 branch
github.com/sars-cov-2-v...
Australia very low circulation with BA.3.2 still leading with low prevalence . Underdogs are XFG.6.13 (.1 or .2) XFG.6.14.1/TC.1 ,PQ.16.1.1, TB.1 ST.1 (both XFG+435S) but also a local PQ.2.1 with 936S and two PLPro mutations could emerge then. RV.1 RF.5 RK.1 already present there too.
July 9, 2026 at 9:23 AM
Australia very low circulation with BA.3.2 still leading with low prevalence . Underdogs are XFG.6.13 (.1 or .2) XFG.6.14.1/TC.1 ,PQ.16.1.1, TB.1 ST.1 (both XFG+435S) but also a local PQ.2.1 with 936S and two PLPro mutations could emerge then. RV.1 RF.5 RK.1 already present there too.
While Nb.1.8.1 +420N is dominating in Singapore and Hk and Growing in South Australia in the batches uploaded today, there is another underdog lineage defined by just a PLPro mutation that keeps going : github.com/sars-cov-2-v... today sampled in HK,Singapore and South Australia
RF.5+Orf1a:T1638N branch (40, circulating in India) with a Orf1b:T730I+ Orf3a:R42L, N:R204Q(9 seqs, 3 places) · Issue #3465 · sars-cov-2-variants/lineage-proposals
RF.5+C5178A(Orf1a:T1638N)+C15656T(Orf1b:T730I), C25517T,G28884A(Orf3a:R42L, N:P204Q) Query for Orf1a:T1638N branch: C5178A,G11851T,C1722T Seqs: 40 ( India, France,Lux, US-5 States, South Korea, THA...
github.com
June 29, 2026 at 1:45 PM
While Nb.1.8.1 +420N is dominating in Singapore and Hk and Growing in South Australia in the batches uploaded today, there is another underdog lineage defined by just a PLPro mutation that keeps going : github.com/sars-cov-2-v... today sampled in HK,Singapore and South Australia
New paper out! We show that SARS-CoV-2 PLpro can be inhibited in a substrate-selective manner, preferentially blocking deISGylation over viral polyprotein processing. Computational modelling suggests a mechanism for the observed substrate selectivity.
Substrate‐Selective Inhibition of the SARS‐CoV‐2 Papain‐Like Protease: Inhibition of Hydrolysis of Human Over Viral Substrates
The SARS-CoV-2 papain-like protease (PLpro) is a medicinal chemistry target. Here we report mass spectrometry assays employing oligopeptide substrates based on the sequences of the viral polyproteins...
chemistry-europe.onlinelibrary.wiley.com
June 16, 2026 at 10:35 AM
New paper out! We show that SARS-CoV-2 PLpro can be inhibited in a substrate-selective manner, preferentially blocking deISGylation over viral polyprotein processing. Computational modelling suggests a mechanism for the observed substrate selectivity.
#SBFM Sunshine Biopharma Announces Issuance of U.S. Patent 12,624,066 B2 Covering Novel Coronavirus Treatment Technology
https://www.stocktitan.net/news/SBFM/sunshine-biopharma-announces-issuance-of-u-s-patent-12-624-066-b2-ptjiese7nusz.html
https://www.stocktitan.net/news/SBFM/sunshine-biopharma-announces-issuance-of-u-s-patent-12-624-066-b2-ptjiese7nusz.html
Sunshine Biopharma Announces Issuance of U.S. Patent 12,624,066 B2 Covering Novel Coronavirus Treatment Technology
Sunshine Biopharma (NASDAQ:SBFM) announced issuance of U.S. Patent 12,624,066 B2 covering proprietary small-molecule compounds for treatment of coronavirus infection. The patent protects PLpro enzyme inhibitors designed to block viral replication and immune suppression. Compounds are ready for GLP studies, the final step before entering clinical trials.
www.stocktitan.net
May 29, 2026 at 12:00 PM
#SBFM Sunshine Biopharma Announces Issuance of U.S. Patent 12,624,066 B2 Covering Novel Coronavirus Treatment Technology
https://www.stocktitan.net/news/SBFM/sunshine-biopharma-announces-issuance-of-u-s-patent-12-624-066-b2-ptjiese7nusz.html
https://www.stocktitan.net/news/SBFM/sunshine-biopharma-announces-issuance-of-u-s-patent-12-624-066-b2-ptjiese7nusz.html
beyond its well-known proteolytic functions such as processing viral polyproteins & stripping ubiquitin or ISG15 from host immune factors. PLpro acts through direct, non-cleavage interactions to hijack specific aminoacyl-tRNA synthetases (aaRSs)
academic.oup.com/jmcb/advance...
academic.oup.com/jmcb/advance...
A non-proteolytic role of SARS-CoV-2 PLpro in modulating host glycyl-tRNA synthetase activity
Jia-Li Lu, Yue Yin, Xiao-Long Zhou; A non-proteolytic role of SARS-CoV-2 PLpro in modulating host glycyl-tRNA synthetase activity, Journal of Molecular Cel
academic.oup.com
May 17, 2026 at 6:19 PM
beyond its well-known proteolytic functions such as processing viral polyproteins & stripping ubiquitin or ISG15 from host immune factors. PLpro acts through direct, non-cleavage interactions to hijack specific aminoacyl-tRNA synthetases (aaRSs)
academic.oup.com/jmcb/advance...
academic.oup.com/jmcb/advance...
#Medsky🧪 #IDsky #publichealth @academic.oup.com
#SARSCoV2 Papain-like protease (PLpro) plays a critical, non-proteolytic role in enhancing host glycyl-tRNA synthetase (GARS1) activity which serves as a strategy to finetune the host translation machinery for viral adaptation
The study reveals that
#SARSCoV2 Papain-like protease (PLpro) plays a critical, non-proteolytic role in enhancing host glycyl-tRNA synthetase (GARS1) activity which serves as a strategy to finetune the host translation machinery for viral adaptation
The study reveals that
May 17, 2026 at 6:19 PM
#Medsky🧪 #IDsky #publichealth @academic.oup.com
#SARSCoV2 Papain-like protease (PLpro) plays a critical, non-proteolytic role in enhancing host glycyl-tRNA synthetase (GARS1) activity which serves as a strategy to finetune the host translation machinery for viral adaptation
The study reveals that
#SARSCoV2 Papain-like protease (PLpro) plays a critical, non-proteolytic role in enhancing host glycyl-tRNA synthetase (GARS1) activity which serves as a strategy to finetune the host translation machinery for viral adaptation
The study reveals that
AVITHRAPID Highlights
Last week in Naples, Prof. Vincenzo Summa (Federico II) presented our latest research at the "Italo-French Chair" Final Workshop!
Key focuses:
🔹 PLpro Target progress
🔹 Dengue Clinical Trial updates
Last week in Naples, Prof. Vincenzo Summa (Federico II) presented our latest research at the "Italo-French Chair" Final Workshop!
Key focuses:
🔹 PLpro Target progress
🔹 Dengue Clinical Trial updates
April 3, 2026 at 1:25 PM
AVITHRAPID Highlights
Last week in Naples, Prof. Vincenzo Summa (Federico II) presented our latest research at the "Italo-French Chair" Final Workshop!
Key focuses:
🔹 PLpro Target progress
🔹 Dengue Clinical Trial updates
Last week in Naples, Prof. Vincenzo Summa (Federico II) presented our latest research at the "Italo-French Chair" Final Workshop!
Key focuses:
🔹 PLpro Target progress
🔹 Dengue Clinical Trial updates
The final speaker of the 2026 Mutational Scanning Symposium is Melissa Call from WEHI (Walter and Eliza Hall Institute of Medical Research). Her talk is covering how mutational profiling of SARS-CoV-2 PLpro exposes inhibitor escape routes.
#VariantEffect26
#AtlasOfVariantEffectsAlliance
#VariantEffect26
#AtlasOfVariantEffectsAlliance
March 27, 2026 at 3:09 AM
The final speaker of the 2026 Mutational Scanning Symposium is Melissa Call from WEHI (Walter and Eliza Hall Institute of Medical Research). Her talk is covering how mutational profiling of SARS-CoV-2 PLpro exposes inhibitor escape routes.
#VariantEffect26
#AtlasOfVariantEffectsAlliance
#VariantEffect26
#AtlasOfVariantEffectsAlliance
Indian Institute of Technology Kanpur scientists find a SARS-CoV-2 protein PLpro directly breaks epithelial barriers, triggering stress inflammation and cell death across flies and mammalian cells, revealing a key driver of COVID-19 tissue damage.
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
www.biorxiv.org
March 26, 2026 at 3:42 AM
Indian Institute of Technology Kanpur scientists find a SARS-CoV-2 protein PLpro directly breaks epithelial barriers, triggering stress inflammation and cell death across flies and mammalian cells, revealing a key driver of COVID-19 tissue damage.
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
SARS-CoV-2 PLpro Drives Epithelial Barrier Disruption Across Drosophila and Mammalian Epithelia https://www.biorxiv.org/content/10.64898/2026.03.24.713966v1
March 26, 2026 at 3:30 AM
SARS-CoV-2 PLpro Drives Epithelial Barrier Disruption Across Drosophila and Mammalian Epithelia https://www.biorxiv.org/content/10.64898/2026.03.24.713966v1
SARS-CoV-2 PLpro Drives Epithelial Barrier Disruption Across Drosophila and Mammalian Epithelia https://www.biorxiv.org/content/10.64898/2026.03.24.713966v1
March 26, 2026 at 3:30 AM
SARS-CoV-2 PLpro Drives Epithelial Barrier Disruption Across Drosophila and Mammalian Epithelia https://www.biorxiv.org/content/10.64898/2026.03.24.713966v1