Specific Mpro (3CLpro or NSP5)
inhibitors
PLpro inhibitors
Exonuclease inhibitors (EI)
Nucleotide inhibitors (NI)
(selective RdRp inhibitors)
4’-modified nucleoside drug candidates
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Small molecular compound
PAXLOVID= Nirmatrelvir (PF-07321332, NMV) + Ritonavir (as a
pharmacokinetic enhancer)
9,10-dihydrophenanthrenes
peptidomimetic
YH-53 (compounds)
GC376, boceprevir, calpain inhibitors II, and XII,
Chloroquine (CQ) & Hydroxychloroquine (HCQ), peptide inhibitors and
GRL0617
Pibrentasvir & Ombitasvir
Remdesivir, Sofosbuvir, Lopinavir, Favipiravir, Molnupiravir & AT-527
FNC (azvudine)
islatravir
balapiravir
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Inhibit the viral target Mpro, an orally administrated
inhibition of viral replication and its survival in the host cell,
a potent and selective inhibitor of the SARS-CoV-2 main protease
(Mpro), lack of genetic toxicity.
Inhibit the viral target PLpro, regulate viral replication;
dysregulates host immune sensing by viral polypeptide cleavage,
de-ISGlyation and immune suppression.
Inhibit the viral target RdRp. Oct 2020, the US FDA approved remdesivir
as the first drug for the treatment of Covid-19
better therapeutic efficacy than remdesivir.
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main protease (3C-Like protease), covalent inhibitors of
3CLpro, a better selectivity index than remdesivir, no
clinically relevant risks associated with PAXLOVID administration.
Papain-like protease
broad-spectrum prodrugs
Due to CV adverse drug reactions (CV-ADRs), need adequate CV
monitoring
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Specific
inhibitors
of RdRp and Nsp15/EndoU, and others
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Alectinib
Naldemedine & Ergotamine
Stapled peptides
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for RdRp
for NSP15
mimic Helix 1 of the human ACE2 receptor
other several kinases including CMGC, CK2, CDK, PKC, PIKFYVE, and
EIF2AK2
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Various signaling pathways including MAPK, GFR signaling, TGF-β,
autophagy, and AKT.
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Specific
anti- hepatitis C virus (HCV) drugs
Anti-HIV drugs
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neoechinulin B (1a)
N3G, a mimetic of the HIV-1 gp41 HR1 trimer
anti-HIV-drug-vitamin c derivatives cocktails
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inactivating the liver X receptors (LXRs), antiviral activities against
HCV & SARS-CoV-2
Inhibit infection of HIV-1 & human β-coronaviruses by blocking the
hexameric structure formation
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a prenylated indole diketopiperazine alkaloid
β-coronaviruses (MERS-CoV, HCoV-OC43 & SARS-CoV-2)
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Antimalarial drugs
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Mefloquine
chloroquine (CQ)/
hydroxychloroquine (HCQ)
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inhibit SARS-CoV-2 replication & reduce SARS-CoV-2 entry
against SARS-CoV-2 PLpro
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An orally available host-acting agent
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Adjunctive treatment
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Melatonin (a low dose),
9 mg daily, orally for 14 days.
Methylprednisolone (MP)
Chitosan and its derivatives
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its anti-oxidation, anti-inflammation by inflammasome activation, and
improvements of immune and clinical symptoms.
reduce inflammation reaction and tissue damage
direct antiviral activity as vaccine adjuvants
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reduce the levels of TNF-α, IL-1β cytokines, MDA, and NO levels, and
significantly increase SOD level.
bradycardia on the premise of the long-term use of arbidol
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Nanotechnology
(Nanomaterials)
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personal protective equipment
anti-viral nano-coats,
nano-based vaccines
nanomaterial-based point-of-care devices
agents carriers
gene editing agents
therapeutic agents
ZnO nanoparticles
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based on modifiable engineering materials and useful physicochemical
properties,
nanobubble ozonated hyaluronic acid-decorated liposomal (NOHAL)
solution
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possible unintended immunotoxicity,
through the nose and/or oral cavity.
ZnONPs
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Botanical Drugs
or
medicinal plants
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plant chemicals:
Artemisia annua L.
Angeloylgomisin O Schisandrin B
Vitex negundo L. (VNL)
Kabasura kudineer Nilavembu kudineer
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phytomedicine-based therapies, effectively inhibit SARS-CoV-2 entry
adjuvant therapeutic agent & a single source of a cocktail of Mpro
inhibitors
the two most widely approved formulations to treat COVID-19.
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Lower side effects, combination with remdesivir
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MNPs
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Gallinamide A
Seaweed’s bioactive compounds
Microalgal metabolites
(carotenoids and lipids)
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directly interacted with cathepsin L in cells
can inhibit the omicron variant
anti-inflammatory properties
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broad-spectrum target inhibition by marine natural products
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TCM or
Herbal medicine
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Jinzhen granule (JZ)
(gallic acid 1.97 mg/g, baicalin 20.69 mg/g, glycyrrhizic acid 4.92
mg/g, hyodeoxycholic acid 4.86 mg/g, cholic acid 4.07 mg/g)
A combination of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules
Baidu Jieduan granules
Bufei Huoxue (BFHX)
Jinhua Qinggan granule (JHQG)
Keguan-1
Lianhua Qingwen (LHQW)
Maxingshigan-Weijing decoction (MWD)
Reduning injection
Reyanning mixture
Shenhuang granule
Shufeng Jiedu capsule (SFJDC)*
Xiyanping (XYP) injection
Plant secondary metabolites or herbal bioactives
(e.g., Green tea extract)
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antiviral activity by
inhibition of main protease and endoribonuclease (NSP15), regulating the
NF-κB/MAPK pathway and the mitochondria-mediated apoptotic pathway.
antiviral, anti-inflammatory, and immunoregulatory activities in acute
lung injury, reduce the use of antibiotics and glucocorticoids, improve
LPS-induced ALI by reducing inflammation and pulmonary vascular
endothelial injury, safe and effective for patients with mild to
moderate COVID-19, especially when combined with conventional western
medicine.
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An alternative treatment
Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2
times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in
boiling water and take after meals, 8 g/time, 2 times/day, a course of 5
days, followed up for 14 days, respectively.
*A patented herbal drug composed of eight medicinal plants.
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Macrolide antimicrobial agents
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Clarithromycin
Azithromycin
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An immunomodulating drug and suppresses cytokine storms in viral
respiratory diseases (including influenza)
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Monotherapy or combination, but may induce QT long and malignant
arrhythmias
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Others:
Multi-targeted anti-viral drugs
Combinations in Covid-19 management
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three alkaloids (lycorine, emetine, and cephaeline)
Such as iota carrageenan nasal spray, ermectin oral drops, omega-3
supplementation, and a quadruple treatment of zinc, quercetin,
bromelain, and vitamin C.
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inhibitors of viral entry
The comprehensive effects of logical combinations with different
mechanisms of action.
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target N-terminal domain (NTD) of nucleocapsid protein (NPro) to inhibit
the replication
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